Tips from Other Journals
Pathogens Associated with Infected Dog and Cat Bites
Approximately 300,000 visits are made to emergency departments in the United States each year for management of animal bites, usually cat or dog bites. Up to 10,000 hospital admissions and 20 deaths may occur in cases of secondary infection, usually in young children. Noted bacterial pathogens include streptococcal and staphylococcal species, as well as Pasteurella multocida and Capnocytophaga canimorsus. Knowledge of the bacteriology of animal bites may have a significant impact on selection of empiric antibiotic therapy and subsequent morbidity and mortality. Talan and colleagues performed a multicenter, prospective study to identify the bacteria responsible for infections in cat and dog bites.
Eighteen university-affiliated emergency departments in the United States participated. Patients were included in the study if the cat or dog bite was large enough to perform a deep culture. Major criteria for infection included at least one of the following: the presence of fever, abscess formation or lymphangitis. Minor criteria (four of five were required for inclusion) were wound erythema greater than 3 cm (1.2 in), tenderness, swelling, purulent drainage or a white blood cell count of more than 12,000 per mm3 (12.0 × 109 per L). Patients who had taken antibiotics within 72 hours of presentation or who had a fracture or radiographically confirmed osteomyelitis were excluded. Aerobic and anaerobic specimens were cultured from the wounds using swabs or needle aspiration. All specimens were sent to the hospital laboratory and a second, standard-reference laboratory. The specimens were incubated for two weeks to permit growth of fastidious organisms.
A total of 107 patients were evaluable, including 50 with infected dog bites and 57 with infected cat bites. The patients ranged from one to 82 years of age, and most bites occurred on the hands and arms. Eighty-five percent of the cat bites and 60 percent of the dog bites were puncture wounds.
The median time for evidence of infection for the cat bites was 12 hours compared with 24 hours for dog bites. The median interval for specimen collection was 25 hours after the bite occurred. The median number of bacterial isolates from the wounds was five, with a range of zero to 16. The most common pathogen was Pasteurella species, occurring in 50 percent of dog bites and 75 percent of cat bites. Other common isolates included Streptococcus, Staphylococcus, Moraxella and Corynebacterium species, as well as a large number of anaerobes. Eikenella corrodens, a pathogen found in human bite wounds, was isolated from one cat bite and one dog bite. A significantly larger number of bacterial isolates were identified at the reference laboratory compared with the hospital laboratories. A variety of antibiotics were used to treat these patients, but most regimens included a beta-lactam drug plus a beta-lactamase inhibitor.
The authors conclude that most cat and dog bites that become infected are complex, polymicrobial infections. Infected bites may also contain organisms not routinely identified by a hospital laboratory. It is therefore suggested that empiric antimicrobial therapy include a beta-lactam antibiotic and a beta-lactamase inhibitor, a second-generation cephalosporin with anaerobic activity, penicillin plus a first-generation cephalosporin, or clindamycin and a fluoroquinolone.
JEFFREY T. KIRCHNER, D.O.
Talan DA, et al. Bacteriologic analysis of infected dog and cat bites. N Engl J Med January 14, 1999;340:85-92.
Fluoxetine for Treatment of Panic Disorder
Although panic attacks are an essential feature of panic disorder, other psychiatric symptoms, such as phobic avoidance, anxiety, depression and obsessions, may also be present in panic disorder. Most studies have focused on the frequency of panic attacks as the principle measure of the severity and outcome of panic disorder, despite growing consensus on the importance of focusing on a wider spectrum of symptoms. Because selective serotonin reuptake inhibitors (SSRIs) have significant antidepressant and anxiolytic actions, it is likely that they provide improved clinical outcomes by reducing the frequency of panic attacks and improving mood and phobic symptoms. Michelson and associates studied the effect of fluoxetine treatment in patients who were diagnosed with panic disorder.
A total of 243 patients were randomly assigned to daily treatment with either 10 mg or 20 mg of fluoxetine, or placebo. Primary outcomes measured were changes in the frequency of panic attacks and clinical symptoms associated with the disorder. Symptom change was assessed by clinician-rated Clinical Global Impression scores. The study included an initial single-blind, placebo lead-in phase, followed by a 10-week acute phase with randomization. Patients who completed the 10 weeks and showed improvement could enter a 24-week continuation phase of treatment with either fluoxetine or placebo. The primary outcome measured in this phase was relapse rate.
Overall response to treatment as assessed by clinical parameters was significantly greater in patients treated with 20 mg (but not 10 mg) per day of fluoxetine than in those treated with placebo. The comparison of placebo and combined fluoxetine treatment also favored fluoxetine. Patients treated with either dosage of fluoxetine experienced a significant reduction in the total frequency of panic attacks compared with the placebo group. The three groups did not differ significantly in the number of patients who were completely panic-free at the last visit of the acute phase.
Anxiety was significantly reduced in the patients treated with 20 mg (but not 10 mg) per day of fluoxetine compared with the patients treated with placebo. Likewise, depressive symptoms were significantly reduced in both fluoxetine groups compared with the placebo group. Phobic avoidance was similarly reduced in either group taking fluoxetine. Patient-rated overall improvement of symptoms was significantly greater in the group taking 20 mg per day of fluoxetine than the group taking placebo.
In addition, repeated analysis of symptom relief in the continuation phase of the trial demonstrated that more patients treated with fluoxetine experienced improvement than those treated with placebo. In the two phases of the trial, both dosages of fluoxetine were well tolerated. Discontinuation rates were similar in the fluoxetine and placebo groups.
Results of this study suggest that fluoxetine is safe and effective in the acute and continuation treatment phases of panic disorder. Treatment with either 10 mg or 20 mg per day of fluoxetine was associated with significantly greater reduction in the total number of panic attacks than treatment with placebo. In addition, treatment with the higher dosage (20 mg per day) of fluoxetine was also associated with a significant reduction in anxiety, phobia and depression.
The authors conclude that a reduction in the frequency of panic attacks does not adequately reflect improvement as a primary measure of psychiatric disease. Clinical improvement in panic disorder is better reflected by a multidimensional approach to symptom control. Better outcomes are achieved if a broader focus on symptom relief is maintained by the treating physician.
BARBARA APGAR, M.D., M.S.
Michelson D, et al. Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. Am J Psychiatry November 1998;155:1570-7.
Beer, Wine or Liquor and the Risk of Myocardial Infarction
The beneficial effect of alcohol consumption on reducing the risk of coronary heart disease seems to be largely related to alcohol's direct effect of increasing the high-density lipoprotein (HDL) cholesterol level, decreasing platelet aggregation or clotting, and enhancing fibrinolysis. Studies have yielded conflicting results as to whether greater benefits are derived from drinking wine, beer or liquor. Gaziano and associates studied the relationship between the type of alcoholic beverage and the incidence of myocardial infarction in a case-control study of 340 patients admitted to the hospital because of myocardial infarction.
A control subject of the same age was matched with each case, providing a total of 340 case-controlled pairs. All case and control subjects were interviewed in their homes; in the case subjects, the interviews occurred approximately 10 weeks after myocardial infarction. Information was collected on various pre-existing risk factors, including diet and alcohol consumption. Of the 680 case and control subjects, 199 were classified as nondrinkers (less than one drink per month), and 331 were classified as regular drinkers (average consumption of more than one-half drink per day). Of the 331 drinkers, 62 preferred wine, 89 preferred beer and 160 preferred liquor. In addition to information about risk factors, lipid profiles were obtained for 160 nondrinkers and 217 regular drinkers.
As would be expected, the proportions of known risk factors for coronary heart disease were higher among study subjects with a myocardial infarction compared with control subjects. Previous alcohol consumption was significantly lower among case subjects. Compared with nondrinkers, regular drinkers of wine, beer or liquor had higher age- and sex-adjusted total HDL cholesterol levels. The risk of myocardial infarction adjusted for age and sex was significantly reduced in regular drinkers of any alcoholic beverage. The age- and sex-adjusted relative risk of myocardial infarction was 0.54 for any drink, 0.48 for wine, 0.55 for beer and 0.59 for liquor. The risk factoradjusted model demonstrated relative risks of 0.58, 0.58, 0.75 and 0.50 for any alcoholic drink, wine, beer and liquor, respectively.
The authors conclude that there is an inverse association between wine, beer and liquor consumption and the risk of myocardial infarction, which may be mediated by HDL cholesterol level. The data from their study suggest that ethanol in alcoholic beverages, rather than other constituents, is responsible for the reduced risk of myocardial infarction.
RICHARD SADOVSKY, M.D.
Gaziano JM, et al. Type of alcoholic beverage and risk of myocardial infarction. Am J Cardiol January 1, 1999;83: 52-7.
Oral Cephalexin or Topical Mupirocin for Wound Infections
Systemic antibiotics are routinely used to treat infection in wounds such as lacerations and abrasions. Kraus and colleagues evaluated the efficacy of oral cephalexin and topical mupirocin cream in the treatment of such wounds. Mupirocin cream is a relatively new formulation of mupirocin and is often preferred over the ointment form because the cream may be used on wounds that should be kept dry.
The randomized double-blind trial was conducted at 53 locations in the United States. The 706 patients in the study had infections of lacerations (up to 10 cm [4 in] in length), abrasions (up to 100 cm2 [15.5 in2] in area), scratches, biopsy sites or body-piercing sites. Excluded were patients who had infections, such as cellulitis, abscess and bite wounds, that would not ordinarily be treated with a topical antibiotic.
A total of 349 patients received oral cephalexin, and 357 received mupirocin cream; 478 were considered evaluable at the end of the study. Oral cephalexin was administered in a dosage of 250 mg four times daily; patients weighing less than 40 kg (88 lb) received a dosage of 25 mg per kg per day in four divided doses. Mupirocin cream (2 percent) was applied three times daily. Each patient also received the placebo form of the other medication (i.e., placebo capsules if mupirocin cream was used or placebo cream if oral cephalexin was used).
A Wright stain (to check for white blood cells from the wound exudate) was performed two days before treatment was instituted. The wounds were examined after three to five days of therapy and again two to three days after completion of treatment. A final bacteriologic evaluation was performed seven to 12 days after completion of the medication. Clinical response was defined as "complete resolution" or "sustained improvement" without the need for further treatment. "Clinical recurrence" was judged to have occurred in patients who required additional antibiotic. Response to treatment was classified as "unable to determine" if a valid evaluation could not be completed. Adverse reactions were recorded.
Treatment was successful in 95 percent of the patients in both groups. Treatment failure occurred in 12 of the 245 patients in the mupirocin group (4.9 percent) and in 11 of the 233 patients in the cephalexin group (4.7 percent). Similar microorganisms were recovered in each group; the bacteriologic success rate was 97 percent in the mupirocin group and 99 percent in the cephalexin group. The incidence of adverse events did not differ statistically in the two groups: 7.6 percent in the mupirocin group and 9.5 percent in the cephalexin group.
The authors conclude that mupirocin cream is as effective, safe and tolerable as oral cephalexin in the treatment of minor secondarily infected wounds.
GRACE BROOKE HUFFMAN, M.D.
Kraus SJ, et al. Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected wounds. J Fam Pract December 1998;47:429-33.
Adherence to Treatment to Prevent Depression Relapse
Although there are a significant number of medical therapies available for use in depression, treatment remains inadequate in many patients. Studies have shown that up to 85 percent of patients experience a recurrence sometime during their lifetime, and 50 percent will have a recurrence within two years of the initial episode. The goal of the first six to eight weeks of treatment is symptom relief. However, therapy should continue for an additional four to nine months to allow for more complete resolution of the episode and to prevent relapse. The need for long-term maintenance therapy depends on the number of previous episodes. Melfi and colleagues evaluated whether adhering to the current treatment guidelines reduces the likelihood of relapse or recurrence in patients with a history of depression.
Patients eligible for the study had a diagnosis of depression as identified by a review of state Medicaid records from 1989 to 1994. Only patients who had taken a tricyclic antidepressant (TCA) or a selective serotonin reuptake inhibitor (SSRI) were included in the study. Three groups of patients were identified: those who filled fewer than four prescriptions during the acute treatment period; those who switched agents or added a second antidepressant; and those who filled four or more prescriptions throughout the acute treatment period. This last group was considered the "continuous-use" group.
The researchers constructed 30-month episodes for depression care, beginning with a six-month pretreatment period in which patients had no evidence of depression and received no mental health care. The second six months were considered the treatment period, during which time the initial diagnosis was made and medical therapy prescribed. This period included the six to eight weeks of acute treatment and at least an additional four months to allow for continued treatment, consistent with current guidelines. The final 18 months comprised the follow-up period, during which time continuation of medical treatment, adherence to therapy, relapse of depression, evidence of a suicide attempt, psychiatric hospitalization and use of electroconvulsive therapy were evaluated.
Approximately 93 percent of the 4,052 patients who were identified for this study were women; participants ranged in age from 18 to 83 years. Approximately one half of the patients were white and one half were black. All patients received a prescription for a TCA or an SSRI within 30 days of the initial diagnosis. Of these patients, 70 percent filled fewer than four prescriptions during the acute treatment period; 11 percent switched or augmented their prescriptions; and 19 percent met the criteria for the "continuous-use" group.
Overall, 23 percent of patients experienced a relapse during the follow-up period. Patients who had filled fewer than four prescriptions had the greatest rate of relapse, while those in the "continuous-use" group had the fewest number of relapses. Other risk factors for relapse included concurrent use of benzodiazepines and substance abuse.
The authors conclude that in most patients taking medication for major depression, the treatment is inadequate. Premature discontinuation of medication was associated with a 77 percent increase in the rate of relapse or recurrence of the depressive episode. Use of a single medication on a continuous basis results in the greatest reduction in the possibility for relapse.
JEFFREY T. KIRCHNER, D.O.
Melfi CA, et al. The effects of adherence to antidepressant treatment guidelines on relapse and recurrence of depression. Arch Gen Psychiatry December 1998;55:1128-32.
EDITOR'S NOTE: The results of this study are consistent with previously published data regarding the initial length of medical therapy for a depressive illness. The finding that 70 percent of patients do not complete treatment is disturbing. This high rate of noncompliance suggests that perhaps physicians should emphasize the importance of continued therapy and follow-up appointments to better monitor response and compliance.
J.T.K.
Steroids and Response to Flu Vaccine in Pediatric Asthma
Influenza viruses account for a significant number of health care visits and hospitalizations annually, despite the availability of an effective vaccine. Children with asthma are at higher risk for serious sequelae of influenza; therefore, they should be vaccinated annually. However, the vaccination rate in this group of patients is less than 10 percent. Physicians may be reluctant to vaccinate these children because it is believed that patients taking corticosteroids have an impaired response to the vaccine. Consequently, many physicians will not give the vaccine to children having an acute exacerbation of asthma. Fairchok and colleagues evaluated the immunogenicity of the influenza vaccine in children who were taking high-dose prednisone for asthma.
Children between the ages of six months and 18 years who presented to a military pediatric clinic with moderate to severe asthma were eligible for the study. Children who required administration of glucocorticoids comprised the treatment group; those who did not comprised the control group. Exclusion criteria included known contraindications to the influenza virus vaccine, recent glucocorticoid therapy or the use of more than 900 mg per day of inhaled steroids or long-term oral steroids. Children in the treatment group received a five-day course of prednisone (2 mg per kg per day) within 48 hours of enrollment. All children were immunized with the standard trivalent influenza vaccine, and those younger than nine years who had not previously been vaccinated were given a booster four to six weeks later.
Serum samples were obtained at baseline and three to six weeks after the vaccination to measure the presence of three antibodies to the influenza virus. An immunologic response was defined as a fourfold or greater increase in the antibody titer from baseline. A postvaccination titer of at least 1:40 was considered a protective immune response.
Fifty-eight children were enrolled over a three-month period, and 50 ultimately completed the study. Most of the patients were boys about 9.6 years of age. Neither group experienced severe adverse effects, an increase in symptoms, or the need for increased use of medication after receiving the vaccine. All children responded well to the A/H1N1 and A/H3N2 antigens, but rather poorly to the B antigen. There were no significant differences in serologic responses between groups or in the number of children who had protective antibody titers of at least 1:40. Children in the treatment group had a greater overall immunologic response to all three components of the vaccine, although these numbers were not statistically significant.
The authors conclude that high-dose prednisone therapy does not diminish the effectiveness of the influenza vaccine in children with asthma. Because the vaccine does not exacerbate asthma symptoms and, in fact, provides a protective immunologic response, physicians should administer the vaccine concurrently, when indicated, to children who are undergoing treatment of acute asthma.
JEFFREY T. KIRCHNER, D.O.
Fairchok MP, et al. Effect of prednisone on response to influenza virus vaccine in asthmatic children. Arch Pediatr Adolesc Med December 1998;152:1191-5.
Can Echinacea Prevent Upper Respiratory Infections?
Herbal medicines have now reached widespread use in the United States. Of the many popular herbal remedies available, one that has received a great deal of attention is echinacea. Several completely different preparations are referred to as echinacea. Reasons for the differences include: the use of three different species of echinacea (Echinacea purpurea, Echinacea pallida and Echinacea angustifolia); the use of different plant parts; different methods of extracting the active ingredients; and the addition of other plant extracts. While there have been many claims of positive effects from echinacea, the most notable is its potential to prevent upper respiratory tract infections. Melchart and associates performed a double-blind, placebo-controlled, randomized trial to determine whether extracts from the roots of E. angustifolia or E. purpurea are effective in the prevention of upper respiratory tract infections in healthy volunteers.
The study included 302 volunteers who did not have an acute illness at the time of enrollment. They came from four military institutions and one industrial plant in Germany. The participants were given an ethanolic extract from the roots of either E. purpurea or E. angustifolia, or placebo, taken orally for 12 weeks. The observed time until first upper respiratory tract infection was the main outcome measure, as well as the number of participants with at least one infection, global assessment and adverse effects.
The authors found no significant differences among the three groups in regard to onset of first upper respiratory tract infection. The time until occurrence of the first upper respiratory tract infection was 66 days in the E. angustifolia group, 69 days in the E. purpurea group and 65 days in the placebo group. There were also no significant differences among the groups in the number, severity or duration of upper respiratory tract infections or in perceived quality of life. Although more subjects in the treatment groups than in the placebo group believed that they benefited from taking the medication, the E. angustifolia group had more adverse effects, mainly minor gastrointestinal symptoms, headache and dizziness.
The authors conclude that the results of this study do not support the widespread belief that echinacea prevents upper respiratory tract infections. However, the findings point to the need to perform future randomized control trials with a larger number of subjects, over a longer study period and with efforts to reduce the chance that subjects can distinguish active drug from placebo.
JIM NUOVO, M.D.
Melchart D, et al. Echinacea root extracts for the prevention of upper respiratory tract infections. Arch Fam Med November/December 1998;7:541-5.
The Role of Phototherapy for Jaundice in Breast-fed Infants
Despite the well-documented benefits of breast feeding, it is frequently associated with severe jaundice in newborns. When jaundice occurs in breast-fed infants, it tends to have an earlier onset and to be more prolonged. To avoid the development of encephalopathy, most infants with severe hyperbilirubinemia are treated with phototherapy. Tan evaluated the effectiveness of phototherapy in newborns with hyperbilirubinemia.
Otherwise healthy full-term infants with confirmed nonhemolytic neonatal hyperbilirubinemia were eligible for the study. The infants were divided into three groups according to feeding method: the first group consisted of formula-fed infants; the second group consisted of breast-fed infants; and the third group received both types of feeding. Phototherapy was initiated in newborns whose bilirubin concentration was more than 14.9 mg per dL (255 µmol per L), or more than 13 mg per dL (222 µmol per L) within the first 48 hours after birth.
Phototherapy was provided continuously, except during feeding, bathing or provision of nursing care. Bilirubin levels were obtained at baseline and again at 12-hour intervals. Treatment was discontinued when the infant's bilirubin level had decreased to less than 10.8 mg per dL (185 µmol per L) for 24 hours. The shortest duration of phototherapy for any infant was 24 hours. Bilirubin levels were obtained daily for a minimum of two days to ensure that no significant rebound occurred. Hemoglobin and hematocrit levels and infant weight were obtained at baseline and at the end of therapy.
A total of 163 infants were enrolled in the study. Demographic characteristics and bilirubin levels at baseline were similar across groups. The amount of weight loss before the start of therapy was greatest in the breast-fed infants; however, all three groups experienced comparable weight gains during the course of therapy. Phototherapy was highly effective in reducing bilirubin levels in all groups, but the 24-hour decrease and the overall decrease were much less in infants who were breast-fed only. On average, these infants required about 10 more hours of phototherapy than infants in the other two groups. The most rapid response to phototherapy occurred in infants fed both breast milk and formula. Overall, phototherapy was successful in all groups, and no additional therapy was required for rebound hyperbilirubinemia. Notably, jaundice persisted for as long as one month in some of the breast-fed infants, compared with seven to 10 days in the other infants. This impression, however, was subjective, since not all infants were available for long-term evaluation. Even in infants whose random samples of direct bilirubin were obtained, the levels never exceeded 0.6 mg per dL (10 µmol per L).
The author concludes that the severe jaundice that often develops in breast-fed infants requires treatment. Phototherapy was effective in reducing bilirubin levels, but infants who were breast-fed required longer treatment. Supplementing breast milk with formula may improve the response to phototherapy. Therefore, in these infants, interruption of breast feeding does not appear to be necessary.
JEFFREY T. KIRCHNER, D.O.
Tan KL. Decreased response to phototherapy for neonatal jaundice in breast-fed infants. Arch Pediatr Adolesc Med December 1998;152:1187-90.
High- vs. Low-Dose Albuterol for Treatment of Acute Asthma
According to the National Asthma Education Prevention Program, beta agonists are the recommended first-line treatment for asthma. For acute exacerbations, this medication is usually given with aerosolized saline in a dosage of 2.5 to 5 mg every 20 minutes for the first hour. The optimal dosage of albuterol has not been determined by controlled studies, although pediatric data indicate that higher cumulative dosages lead to greater improvement in pulmonary function. In Europe, dosages of 5 to 10 mg are commonly used for treatment of acute asthma. Emerman and colleagues compared the efficacy of 2.5 mg of albuterol with that of 7.5 mg in adults with acute asthma.
Patients enrolled in the study were 18 to 50 years of age and had presented to the emergency department with an acute exacerbation of asthma. Patients with a previous diagnosis of chronic obstructive pulmonary disease, lung surgery or lung cancer were excluded. Also excluded were patients with clinical evidence of pneumonia, congestive heart failure or pneumothorax. Oxygen was given to maintain a saturation of more than 91 percent, and three measurements of the forced expiratory volume in one minute (FEV1) were obtained, with the highest value used as the baseline value. The patients were then randomized in a double-blind fashion to receive either 2.5 or 7.5 mg of nebulized albuterol every 20 minutes for one hour. The patients were also given 60 mg of oral prednisone. Spirometry was obtained after each of the first two treatments and 40 minutes after the third dose of albuterol. The patients were discharged or admitted to the hospital based on spirometry values and the clinical decision of the emergency department physician.
A total of 160 patients were randomized into the study; most of them were women. All of the study subjects had been receiving outpatient therapy for asthma. Most of the study subjects were using beta agonists (84 percent), and significantly smaller percentages of patients were using inhaled steroids, theophylline or oral steroids. Thirty percent of the study subjects were smokers.
The mean pretreatment FEV1 was 36.9 percent of predicted in the low-dose albuterol group and 41.5 percent of predicted in the high-dose group. After three treatments, the final FEV1 was 50.6 percent of predicted in the 2.5-mg group and 56.3 percent of predicted in the 7.5-mg group. These values were not statistically significant, nor were the overall improvements in FEV1 in both groups of patients. Forty-three percent of the patients in the low-dose group and 39 percent in the high-dose group were admitted to the hospital. Almost 50 percent of the patients in the low-dose group complained of nausea, tremor, chest pain, palpitations or headache, compared with 44.2 percent in the high-dose group.
The authors conclude that a 7.5-mg dosage of albuterol offers no apparent clinical advantage to the standard 2.5-mg dosage in the acute treatment of asthma. As shown in previous studies, patients with an inadequate response to the first dosage of albuterol do not respond to an increased dosage and usually require hospital admission.
JEFFREY T. KIRCHNER, D.O.
Emerman CL, et al. Comparison of 2.5 vs 7.5 mg of inhaled albuterol in the treatment of acute asthma. Chest January 1999;115:92-6.
Challenges in Diagnosing the Cause of Breast Pain
Breast pain (mastodynia) can be a difficult condition to manage, and the cause of the pain often remains undiagnosed. Mammography or biopsy (or both) may be used to evaluate the painful area, but the contribution of these investigations is unclear. Duijm and colleagues studied women referred to a Dutch teaching hospital for investigation of breast pain to establish the usefulness of mammography and biopsy in the assessment of breast pain.
A total of 987 women were referred for evaluation of breast pain of unknown etiology. Patients with palpable masses or a history of breast cancer or breast augmentation were excluded from the study. All patients were examined by a radiologist and underwent mammography. Additional views were performed as indicated. Ultrasonography was performed if the mammogram was inconclusive, if breast tissue was dense or if pain was localized to one quadrant in a patient younger than 25 years.
Two years after the initial studies, the study subjects' physicians were asked to complete a questionnaire providing follow-up information on the patients. The researchers also monitored all breast pathology specimens in the region as well as in the national cancer registry to detect any breast cancer or other breast pathology developing in study patients.
The average age of the study subjects was 50.4 years. Unilateral pain was reported by 76 percent of the women, and bilateral pain was reported by 24 percent. Mammography was normal in 86.5 percent of the study subjects and revealed benign abnormalities in 8.6 percent. Only four malignant lesions were detected by initial mammography. Four additional cancers were confirmed by further investigation of mammographically suspicious lesions. At two-year follow-up, the family physicians reported that 948 women were free of breast cancer. Two women developed breast cancer during the follow-up period, three died of unrelated causes and five women could not be traced.
The authors conclude that breast imaging is not useful in diagnosing the etiology of breast pain but may provide reassurance. Radiologic abnormalities are found in few patients with breast pain, and those nonpalpable lesions that are detected are predominantly not clinically significant.
ANNE D. WALLING, M.D.
Duijm LE, et al. Value of breast imaging in women with painful breasts: observational follow-up study. BMJ December 1998;317:1492-5.
Is Early Surgery Preferable to US for Small Aortic Aneurysms?
Abdominal aortic aneurysms are usually asymptomatic until they rupture, at which time they are generally fatal. Unfortunately, most aneurysms are not detected, but in the United Kingdom as many as 3 percent of men older than 60 years are estimated to have small aneurysms (4.0 to 5.9 cm in diameter). Elective surgery is usually advised to repair large aneurysms (6.0 cm or greater) because emergency repair of a ruptured aneurysm has a 30-day mortality rate of 40 to 50 percent, while the mortality rate associated with elective surgery is only 5 to 6 percent. However, there is no consensus on the optimal management of smaller occult aneurysms. The UK Small Aneurysm Trial evaluated elective surgery of small asymptomatic aneurysms to find out if it decreased long-term mortality compared with use of regular ultrasound surveillance (US).
A total of 1,276 otherwise healthy patients between 60 and 75 years of age with small occult abdominal aortic aneurysms were eligible for the four-year study. Patients with aneurysms 4.0 to 4.9 cm in diameter were reviewed every six months, and those with larger lesions were evaluated every three months. Surgical repair was recommended to the patient if the aneurysm exceeded 5.5 cm, if the growth rate exceeded 1 cm per year, if the aneurysm became tender or if other symptoms developed. On average, patients in the study were followed for more than four years.
Of the 1,090 patients who were enrolled in the study, 563 were randomized to receive early surgical intervention and 527 were assigned to surveillance. Of the 563 patients in the surgery group, 452 had surgery within five months of randomization. Of the 527 patients assigned to surveillance, 489 followed the study protocol for surgery. Mortality did not differ between the two groups at two, four or six years, even after adjustment for age, sex or initial size of the aneurysm. After six years, 150 patients in the surveillance group had died and 159 in the surgery group had died. The 30-day mortality rate following surgery was 5.8 percent in the surgery group, compared with 7.1 percent in the surveillance group. Seventeen patients in the surveillance group died from a ruptured abdominal aortic aneurysm, compared with six in the surgery group.
The authors conclude that early surgery does not confer a significant long-term survival advantage in patients with small asymptomatic aortic aneurysms. Use of ultrasonographic surveillance provides a safe alternative for management of this condition. The results of this trial affect screening of patients with small aneurysms. Those with aneurysms smaller than 5.5 cm should be advised to stop smoking and to undergo ultrasonographic surveillance until such a time as surgery is warranted.
ANNE D. WALLING, M.D.
The UK Small Aneurysm Trial Participants. Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet November 21, 1998; 352:1649-55.
Aspirin in Patients with Diabetes Mellitus and CAD
The benefits of aspirin on cardiac morbidity and mortality in patients with coronary artery disease (CAD) are well known. Similar benefits are possible in patients with diabetes mellitus and CAD; however, this population has not been well studied. Harpaz and colleagues evaluated the effects of aspirin on mortality in patients with type 2 (non insulin-dependent) diabetes mellitus and CAD.
Patients between 45 and 74 years of age who had a documented history of CAD were eligible for the study if they also had a history of diabetes mellitus. Patients with type 1 (insulin-dependent) diabetes were excluded from the study. At the screening visit, blood samples, demographic information, medical history and information about current medications were obtained for all patients. Functional capacity and angina class were also recorded for all patients. Mortality data and cause of death were recorded, with a mean follow-up period of 5.1 years.
Of the approximately 11,000 patients who were screened, 2,368 patients met the criteria for the study. Mean patient age was 60 years, and most of the patients were men (74 percent). Use of aspirin was reported by 52 percent of these patients compared with 56 percent of patients without diabetes. Patients who took aspirin were more like to be younger, male, and to have had a myocardial infarction. Mortality rates in patients with diabetes mellitus were two times higher than in patients without diabetes. However, cardiac and all-cause mortality rates were much lower in patients with diabetes who took aspirin compared with diabetic patients who did not. Overall, the absolute benefit of aspirin use was greater in patients with diabetes and CAD than in the group of CAD patients without diabetes mellitus, even though there was clear benefit in both groups.
The authors conclude that cardiac and all-cause mortality rates are significantly reduced in CAD patients with type 2 diabetes mellitus, and that this benefit is more pronounced than in CAD patients without diabetes mellitus. Unless clearly contraindicated, aspirin should be given to all patients with CAD and type 2 diabetes mellitus.
GRACE BROOKE HUFFMAN, M.D.
Harpaz D, et al. Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease. Am J Med December 1998;105:494-9.
Brief, Practical Screening for Dementia in Outpatients
Routine screening for dementia in elderly patients in the outpatient setting is increasingly recommended as the population ages and the corresponding incidence of dementia increases. Unfortunately, existing screening tests are relatively lengthy or simply too complex to use in a typical outpatient setting. The Time and Change (T&C) test is a simple, yet rapid screening device that assesses a patient's ability to tell time and make change. This test has been previously validated to detect dementia in inpatient populations. Froehlich and colleagues evaluated the validity of the T&C test in an outpatient population.
Briefly, the T&C test includes two tasks: telling time and making change. In the telling time task, patients are shown an analog clock face set at 11:10. Those who are able to tell the time receive a correct rating. In the making change task, patients must make one dollar in change when shown three quarters, seven dimes and seven nickels. Those who can complete the task within two minutes receive a correct rating. Patients are allowed two tries for each task. Incorrect responses on both tasks suggest dementia. A timed cut point test is also performed, with a negative (or "no dementia") rating achieved if the patient can tell the time correctly in one try within three seconds and can make change in one try within 10 seconds.
Patients eligible for the study were at least 75 years old and were selected from a primary care center and a geriatric assessment center. Medical records were also reviewed to identify any documentation of cognitive loss, memory loss or dementia within the past two years. The procedure for validation of the test was as follows: after a patient interview in which demographic information was obtained, patients were given the T&C test, followed by the Mini-Mental State Examination (MMSE) and digit span. Caregivers were given the modified Blessed Dementia Rating Scale (mBDRS). Dementia was defined for this study as either an mBDRS score of greater than four or an mBDRS score of greater than two and an MMSE score of less than 20 with symptoms of cognitive loss for at least six months.
Out of 100 patients who were included in the validation portion of this study, 16 had dementia according to the study definition. Of these 16 patients, 10 scored positive for dementia on the T&C test. Of the 84 patients who did not meet the study definition, 81 scored negative for dementia on the T&C test. Thus, the sensitivity of the test was 63 percent, the specificity 96 percent and the negative predictive value 93 percent. Unlike the MMSE, the T&C test did not appear to be affected by education level. When the timed cut points were used for the telling time task, all 16 patients with dementia were identified as having dementia. In the concurrent validation sample, review of patients' medical records revealed that physicians had identified only nine of the 16 patients with dementia. Four of the remaining seven patients were correctly identified as having dementia on the basis of the T&C test, reducing the percentage of unrecognized patients from 44 to 19 percent. All patients with chart documentation of dementia were also correctly identified with the T&C test.
Detection of dementia is important, since treatment of reversible causes is occasionally possible, new treatments are emerging, and family and patient support may delay certain end points, such as nursing home placement. The authors conclude that the T&C test can be reliably used in an outpatient setting to screen for dementia, particularly in settings where no testing is currently done. However, with a sensitivity of only 63 percent, mild cases may still be missed. Therefore, the performance of the T&C test in patients with mild dementia requires further study. Additional dementia measures should be used in these patients if dementia is suspected.
GRACE BROOKE HUFFMAN, M.D.
Froehlich TE, et al. Screening for dementia in the outpatient setting: the time and change test. J Am Geriatr Soc December 1998;46:1506-11.
EDITOR'S NOTE: One striking aspect of this study is that not one patient refused to complete even a portion of the T&C test. Anyone who has ever administered an MMSE knows that patients often claim that they are "bad at math" or unable to draw or feel that the questions are inappropriate, leaving the physician with incomplete results. A simple screening test such as the T&C test could be useful in determining cognitive loss. However, it must be emphasized that this test should not be used to establish the diagnosis because it has a fairly high rate of false-positive results, especially on the timed portion, which could have devastating consequences to the patient. Therefore, suspected cases of dementia require other diagnostic measures.
G.B.H.
Testosterone Therapy in Boys with Delayed Puberty
While boys with a constitutional delay of puberty eventually have normal activation of the hypothalamic-pituitary-gonadal axis, their sexual immaturity and relative short stature may contribute to psychosocial problems. Androgen therapy, commonly given as a four-month course of testosterone injections, provides a boost in physical growth and maturity. In addition to constitutional delay of puberty, obesity and growth hormone deficiency may cause delayed puberty. Kaplowitz conducted a retrospective study to compare responses to testosterone therapy in boys with delayed puberty from constitutional delay, obesity and possible gonadotropin deficiency.
All of the boys were 14 years of age or older when they received testosterone injections. Twenty-three had constitutional delay of puberty and were of short stature, six had obesity and were of normal stature, five had hypopituitarism and growth hormone deficiency and two had isolated gonadotropin deficiency. They were prepubertal or in early puberty according to both physical characteristics and serum testosterone levels, which were less than 40 ng per dL (1.4 nmol per L). All received a course of testosterone enanthate injections, 100 mg intramuscularly, once a month for four months.
Testosterone therapy resulted in an increase in height and weight velocity in the 23 boys with constitutional pubertal delay. Penis and testicular size also increased during treatment. The six obese boys also had an increase in penis and testicular growth. The five boys with growth hormone deficiency received growth hormone replacement in addition to testosterone injections. Two of these boys had severe gonadotropin deficiency and did not demonstrate increased maturation rates. In two boys, testicular size increased, although not as rapidly as in boys with constitutional delay of puberty.
The author concludes that monitoring the response to testosterone injections in boys with delayed puberty helps to differentiate constitutional delay of puberty from gonadotropin deficiency in boys with delayed puberty. Since a rapid growth rate requires increased androgen and growth hormone production, the response to testosterone augmentation in the boys with constitutional delayed puberty excluded the possibility of growth hormone deficiency. In the obese boys, progression of maturation may have occurred after testosterone injections because of the inhibitory effects of androgens on leptin levels, which are presumed to be inceased in obese adolescent boys. After age 10, as testosterone and gonadotropin levels increase, serum leptin levels normally decline to levels found in boys five to six years of age, suggesting that increasing testosterone levels may inhibit leptin production. The author also believes that a lack of response to four testosterone injections may be useful in identifying boys who require long-term therapy because of gonadotropin deficiency.
In an accompanying editorial, Saenger and Sandberg note that testosterone therapy in boys with delayed maturation may help increase the velocity of maturation, but there is insufficient documentation to show that the psychosocial stress from delayed maturation is severe enough to warrant intervention with testosterone injections. Most of these children have a healthy adaptation, and treatment decisions should be weighed carefully. The authors believe the psychosocial benefit of treating constitutional delay of puberty may be overstated.
RICHARD SADOVSKY, M.D.
Kaplowitz P. Delayed puberty in obese boys: comparison with constitutional delayed puberty and response to testosterone therapy. J Pediatr December 1998; 133:745-9, and Saenger P, Sandberg DE. Delayed puberty: when to wake the bugler [Editorial]. J Pediatr December 1998;133:724-5.
Niacin and Atherosclerotic Cardiovascular Disease
The easily recognizable side effects of niacin seem to have somewhat overshadowed its usefulness in the treatment of hyperlipidemia. To examine the usefulness of niacin in the treatment of atherosclerotic cardiovascular disease, Guyton reviewed data from six major clinical trials in which cardiovascular events were end points. These trials were the Coronary Drug Project, the Stockholm Ischemic Heart Disease Secondary Prevention Study, the Cholesterol-Lowering Atherosclerosis Study, the Familial Atherosclerosis Treatment Study, the Harvard Atherosclerosis Reversibility Project and an unnamed study conducted at the University of CaliforniaSan Francisco.
The first landmark study that used niacin was the multicenter Coronary Drug Project (CDP). Published in 1975, this study was the only one that used niacin monotherapy to affect cardiovascular endpoints. A total of 8,341 men with a previous myocardial infarction were recruited for the six-year randomized trial. Niacin in a dosage of 1 g three times daily was found to decrease cholesterol levels by 10 percent and triglyceride levels by 26 percent. Recurrent nonfatal myocardial infarction was decreased by 27 percent. The frequency of cerebrovascular events was decreased by 26 percent. The cardiovascular mortality risk was also decreased, to a small degree.
The Stockholm Ischemic Heart Disease Secondary Prevention Study was a five-year randomized placebo-controlled trial of 555 consecutive survivors of myocardial infarction. Results of this study demonstrated decreased total and cardiac mortality among men taking a combination of niacin, 1 g three times daily, and clofibrate, 1 g twice daily. Cholesterol levels decreased by 13 percent and baseline triglyceride levels by 19 percent in the treated patients. Total mortality was decreased by 26 percent, which is considered to be the most important finding of this study.
The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled trial of 162 men aged 40 to 59 years who had undergone coronary artery bypass surgery. Cardiovascular endpoints were measured by coronary angiography. Follow-up was for four years in 103 of the men (CLAS II). Patients received combination therapy with niacin and colestipol. In CLAS I, 39 percent of the men receiving niacin and colestipol had progresion of disease, compared with 61 percent of the men receiving placebo. In LAS II, 48 percent of the treated group had progression, compared with 85 percent of the placebo group. Disease regression was noted in 16 percent of the CLAS I subjects and 18 percent of the CLAS II subjects receiving the cholesterol-lowering therapy. With placebo, regression was noted in 2 percent and 6 percent, respectively, of the CLAS I and CLAS II patients,
In the Familial Atherosclerosis Treatment Study (FATS), 146 men with documented coronary artery disease and apolipoprotein B levels of more than 125 mg per dL were included in the 30-month study. Patients were randomly assigned to treatment with 4 g of niacin plus 30 g of colestipol per day or 40 mg of lovastatin plus 30 g of colestipol per day. Patients receiving the combination of niacin and colestipol had a higher increase in high-density lipoprotein (HDL) levels than those receiving lovastatin and colestipol. Regression of coronary stenosis was small and of questionable clinical significance. However, the number of cardiovascular events was significantly lower in the intensive treatment groups: two events among 48 patients receiving niacin and colestipol, three events among 46 patients receiving lovastatin and colestipol and 11 events in 52 patients receiving conventional therapy.
The University of CaliforniaSan Francisco study included 72 patients with familial hypercholesterolemia. In this two-year, placebo-controlled study, patients were assigned to intensive treatment with niacin plus colestipol or lovastatin (when lovastatin became available). Angiographic progression occurred in the control group, but lesions regressed in the treated group. Regression of atherosclerosis occurred despite elevated low-density lipoprotein levels.
The Harvard Atherosclerosis Reversibility Project (HARP) evaluated whether stepped therapy with four lipid-lowering drugs, including niacin, would affect progression of coronary lesions in patients with normal cholesterol levels. Unlike the other studies, HARP did not demonstrate significant differences in lesion progression or in coronary events. The active treatment group did, however, have 33 percent fewer clinical events than the control group.
The side effects of niacin included flushing, stomach pain, nausea, acute gouty arthritis, and a variety of skin problems such as itching, urticaria, hyperpigmentation and rashes. Other less common adverse symptoms included dysuria, polyuria, anorexia and unexpected weight loss. Niacin can also cause increases in aspartate aminotransferase, alkaline phosphatase, creatine kinase, glucose and uric acid levels.
The author concludes that the results of these clinical studies demonstrate statistically significant benefit from niacin in patients with atherosclerotic disease. Only one of the studies used niacin monotherapy, but this study was by far the largest. The author also points out that the benefits were observed in studies that did not necessarily recruit patients with dyslipidemia. Niacin may be most useful in patients with high triglyceride, low HDL cholesterol and high lipoprotein(a) levels.
RICHARD SADOVSKY, M.D.
Guyton JR. Effect of niacin on atherosclerotic cardiovascular disease. Am J Cardiol December 17, 1998;82:18U-23U.
EDITOR'S NOTE: A new extended-release niacin (Niaspan) allows a once-daily dosage. Used as monotherapy or in combination, niacin has been found to reduce LDL cholesterol levels and increase HDL cholesterol levels. Triglyceride and lipoprotein(a) levels can also be significantly reduced. The extended- release niacin frequently causes flushing, but this side effect can be reduced with concomitant aspirin. Flushing often decreases over several months. Elevation of liver enzymes occurs with niacin but hepatotoxity is rare. The combination of sustained-release niacin and a statin appears to be safe and effective as long as the patient is monitored for the development of myopathy and hepatic inflammation.
R.S.
Blood Pressure Control by Physicians is Inadequate
Even though hypertension is one of the most common reasons for visits to a physician's office, many patients have poorly controlled hypertension. Data from the National Health and Nutrition Examination Survey found that only 24 percent of patients with hypertension had blood pressures of less than 140/90 mm Hg. Research has shown that management of hypertension is inadequate even among patients who receive regular medical care. Patient noncompliance has often been the focus of studies, while the role of the physician in management, particularly in prescribing different medications, has not. Berlowitz and colleagues evaluated the way physicians managed hypertension in patients who had direct access to health care and medications in an effort to develop recommendations for improving care.
Patients were eligible for this multi-center trial conducted at five Veterans Administration outpatient clinics if they had been seen by a physician at least three times at specified intervals over a two-year period. Patients' medical records were reviewed to obtain information regarding the reason for the visit, symptoms, diagnoses and physical findings, including blood pressure measurements, test results and medications prescribed. Information regarding changes in dosage or type of medication was obtained from physician orders, progress notes and pharmacy records. A blood pressure of less than 140/90 mm Hg was considered well controlled; a systolic pressure over 160 mm Hg or a diastolic pressure over 95 mm Hg was considered poorly controlled.
Eight hundred men were evaluated for the study. The mean patient age was 65 years, and approximately 90 percent of the patients were white. At baseline, the mean systolic blood pressure was 146 mm Hg; after two years of medical care, it was relatively unchanged at 145 mm Hg. Mean diastolic blood pressures were relatively unchanged as well, decreasing only slightly from 84.3 to 82.6 mm Hg during this same time. However, during this time the percentage of patients with a baseline blood pressure of greater than 160/90 mm Hg decreased from 46 to 39 percent.
Despite these rather poor results, patients, on average, visited a physician six times over the two-year study period. Antihypertensive medications were increased at 6.7 percent of the visits, most commonly when the patient's diastolic blood pressure was greater than 90 mm Hg, although changes in therapy were instituted at only 35 percent of all visits. Changes in therapy were rare if patients' blood pressure was less than 160/90 mm Hg and there was no history of coronary artery disease. An intensity score was calculated to quantify the degree of medical therapy. Patients who had the highest intensity scores had the greatest mean decreases in both systolic and diastolic blood pressures during the two years of follow-up.
The authors conclude that many patients with hypertension have inadequate control of blood pressure. In this population, fewer than 25 percent had readings of less than 140/90 mm Hg. Clearly, lack of access to care and medications were not issues in this population. Noncompliance may be to blame, at least in part, but was not specifically addressed in this study. Rather, physician prescribing behavior was examined. Physicians in this study frequently failed to change dosages or introduce new medications to better control hypertension. Data from this study suggest that physicians should continually reassess their approach to individual patients and consider more aggressive therapies to control of blood pressure.
JEFFREY T. KIRCHNER, D.O.
Berlowitz DR, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med December 31, 1998;339:1957-63.
EDITOR'S NOTE: The message of this study is fairly straightforward: physicians are not aggressive enough in treating hypertension, despite the availability of national treatment guidelines, access to care and an almost infinite number of antihypertensive medications. Patient compliance certainly is a contributing factor, but it appears that our approach to treatment is simply not aggressive enough. Educating patients about the importance of following treatment regimens is a strength of managed care organizations. Fixed-combination therapies given once daily are reestablishing themselves and may provide at least a partial solution to this problem.
J.T.K.
What Is the Appropriate ACE Inhibitor Dosage in CHF?
The use of angiotensin converting enzyme (ACE) inhibitors has been shown to significantly decrease rates of morbidity and mortality in patients with congestive heart failure (CHF). Most studies support the use of high-dose ACE inhibitors, but the clinical data indicate that only 25 percent of patients with CHF were receiving full dosages of their ACE inhibitors, despite recent recommendations that high-dose ACE inhibitor therapy should be the goal in CHF treatment. Van Veldhuisen and associates studied the dose-related effects of three dosages of a long-acting ACE inhibitor in patients with mild to moderate CHF.
Patients with mild to moderate CHF (New York Heart Association classes II and III) were enrolled in the 12-week study. All of the patients were stable and were undergoing therapy with digoxin and diuretics. A double-blind, placebo-controlled study was performed, with the treatment groups receiving 2.5, 5 or 10 mg of imidapril. Exercise testing was performed twice at baseline and at weeks 8 and 12 of the study. Plasma neurohormones were measured at rest and at the peak of the exercise test.
The initial results showed that after eight weeks no significant differences were apparent between the various treatment and placebo groups. However, at week 12, the group that was taking 10 mg of imidapril had a significant improvement in exercise time and physical walking capacity. The increasing ACE inhibitor dosage also had a positive impact on plasma neurohormones that followed a linear pattern.
Even though high-dose ACE inhibitor therapy is indicated in the treatment of CHF, clinicians tend to use lower dosages. Inadequate dosing could be a result of concerns about increasing adverse events with higher dosages.
The authors conclude that, despite these concerns, patients showed a significant improvement in functional status with a short course of high-dose ACE inhibitors. They believe that even though this was a short study and further studies are needed to confirm these results, high-dose ACE inhibitors should be used in the treatment of mild to moderate CHF.
KARL MILLER, M.D.
Van Veldhuisen DJ, et al. High- versus low-dose ACE inhibition in chronic heart failure. A double-blind, placebo-controlled study of imidapril. J Am Coll Cardiol December 1998;32:1811-8.
Use of Haloperidol in Alzheimer's Disease
Nearly one half of patients with Alzheimer's disease may experience psychomotor agitation. Untreated psychosis and disruptive behaviors are distressing to both patients and caregivers, and may force institutionalization. A meta-analysis has suggested the moderate superiority of neuroleptic agents over placebo in the treatment of psychosis and agitation in patients with dementia. However, neuroleptics are poorly tolerated by patients with Alzheimer's disease. Devanand and associates performed a randomized, double-blind, placebo-controlled trial of haloperidol and placebo to determine the optimal dosage of haloperidol to treat patients who have Alzheimer's disease with psychosis and disruptive behaviors.
During the six-week trial, 71 outpatients with Alzheimer's disease were randomized to receive a "standard" dosage of haloperidol (2 to 3 mg per day), a "low" dosage of haloperidol (0.50 to 0.75 mg per day), or placebo. The standard dosage range was toward the high end of dosages used clinically but was also below the dosage of 5 mg per day that often results in severe extrapyramidal signs. In a subsequent six-week cross-over phase, patients who were taking haloperidol were switched to placebo, and those who were taking placebo were switched to haloperidol.
Analyses indicated that in all measures of efficacy, therapeutic effects were greater with the standard dosage of haloperidol (55 to 60 percent rate of response) than with either the low dosage of haloperidol (25 to 35 percent rate of response) or placebo (25 to 30 percent rate of response). Significant differences were seen in patients taking the standard dosage in the reduction of psychosis and psychomotor agitation, but not in physical aggression and hostility/suspiciousness.
Extrapyramidal signs tended to be greater with the standard dosage of haloperidol than with the low dosage or placebo. Twenty percent of the patients in the group taking the standard dosage developed moderate to severe extrapyramidal signs.
Forty-nine patients entered the cross-over phase. Patients who switched from placebo to standard dosage therapy showed nonsignificant superiority to the low dosage group in physical aggression, psychomotor agitation, hostility/suspiciousness and psychosis. The patients first treated with haloperidol who switched to treatment with placebo demonstrated a partial reversal of the improvement that was noted in the acute phase. Patients who switched to placebo after six weeks of standard-dose haloperidol displayed worsening symptoms, indicating that a longer period of treatment is necessary before discontinuation of medication should be attempted.
The authors conclude that the use of 2 to 3 mg per day of haloperidol leads to an acceptable trade-off between efficacy and side effects for psychotic or agitated patients with Alzheimer's disease, except in those who develop moderate to severe extrapyramidal signs. Dosages below 1 mg per day are ineffective. There appears to be a narrow therapeutic window for patients with Alzheimer's disease who are treated with haloperidol that may also apply to other neuroleptic agents. Since many patients who received 2 to 3 mg per day of haloperidol developed moderate to severe extrapyramidal signs, a starting dosage of 1 mg per day with gradual upward dosage adjustments is recommended. Close monitoring is needed to ensure the efficacy and safety of the treatment.
BARBARA APGAR, M.D., M.S.
Devanand DP, et al. A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. Am J Psychiatry November 1998;155:1512-20.
Osteoporosis and Risk of Fracture: When to Treat?
The Fracture Intervention Trial was designed to study the effects of alendronate in increasing bone density and reducing the risk of vertebral fracture in women with low bone mineral density. The trial studied two groups of women: the first group had had vertebral fractures; the second had not. In this part of the study, Cummings and associates evaluated the effectiveness of four years of treatment with alendronate in reducing the risk of clinical fractures in postmenopausal women with osteoporosis but no history of vertebral fractures.
Patients were included if their femoral neck bone mineral density was 0.68 g per cm2 or approximately two standard deviations below the mean for normal young white women. Exclusion criteria included a recent history of severe hypertension, myocardial infarction, peptic ulcer, dyspepsia, significant renal or hepatic dysfunction, or a recent history of taking estrogen, calcitonin, bisphosphonates or fluoride. However, about 10 percent of the women in this study took estrogen at some point during the study period.
Patients were randomized to receive either placebo or alendronate, with an initial dosage of 5 mg daily, increasing to 10 mg daily during the second year. Height and total body bone mineral density were measured at baseline and at the end of the study. Follow-up visits were conducted twice yearly, at which time patients reported any instance of clinical fracture confirmed by a physician and any adverse health events that may have occurred. Pathologic fractures and fractures related to trauma were not included.
A total of 4,432 women were included in this part of the study, with 2,214 in the alendronate group and 2,218 in the control group. Follow-up was an average of 4.2 years and, at the end of the study period, more than 80 percent of women in each group were still taking their assigned medication. Patients in the alendronate group experienced increases in bone mineral density at multiple sites and had a lower incidence of clinical fractures than patients in the control group. The risk of clinical fractures was related to patients' initial femoral neck bone mineral density, with the greatest benefit of treatment occurring in patients whose initial bone mineral density was lowest. Specifically, women whose initial femoral neck bone mineral density was at least two standard deviations below the mean had a 22 percent lower risk of clinical fracture. In patients with higher BMDs, treatment did not reduce the risk of clinical fracture. The incidence of adverse health effects was not significantly different between groups.
The authors conclude that a four-year course of alendronate decreases the risk of clinical fracture in women with previously low bone mineral density and no vertebral fractures. They note, however, that it is not clear how long the course of alendronate should be continued.
In a related editorial, Heaney discusses some of the difficulties inherent in studying the complexities of osteoporosis and fracture prevention. The most important of these may be the inability to identify, given two patients with identical bone mineral densities, which patient is more likely to sustain a fracture. Fragility appears to be governed by more than just low bone mass, but bone mass is frequently studied, since it is a parameter that can be changed with physician intervention. At present, treatment with bisphosphonates seems to be reasonable in women with a bone mineral density of more than 2.5 standard deviations below the mean, a history of any fracture after age 40, corticosteroid therapy, impending prolonged immobilization or a maternal history of hip fracture. In women at lower risk, other options include estrogen receptor modulators, hormone replacement therapy, and calcium and vitamin D. All women at risk should be encouraged to participate in weight-bearing exercise and to take at least 1,500 mg of calcium and at least 600 IU (up to 1,000 IU) of vitamin D daily.
GRACE BROOKE HUFFMAN, M.D.
Cummings SR, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. Results from the Fracture Intervention Trial. JAMA December 1998;280:2077-82, and Heaney RP. Bone mass, bone fragility, and the decision to treat [Editorial]. JAMA December 1998;280:2119-20.
EDITOR'S NOTE: The National Osteoporosis Foundation has recently issued guidelines calling for osteoporosis screening in all white women over age 65 years. In addition, the foundation recommends bone mineral density testing about every two years in women taking estrogen replacement therapy. The American Academy of Family Physicians does not currently recommend screening with bone mineral density tests but does urge counseling at-risk patients about methods to maintain bone mass. Risk factors for fracture include a history of fracture after 40 years of age; a history of parental fracture after 50 years of age; advanced age; white race; female sex; dementia; frailty; cigarette smoking; weight of less than 57 kg (125 lb); estrogen deficiency; history of low calcium intake; alcoholism; history of recurrent falls; and inactivity.
G.B.H.
Sleep Apnea, Nasal CPAP and Improved Quality of Life
Obstructive sleep apnea is typically characterized by upper-airway obstruction that results in episodic asphyxia, oxygen desaturation and disruption of the normal sleep pattern. Persons with obstructive sleep apnea often have daytime sleepiness with loss of concentration and memory impairment. An additional concern is the potential for cardiovascular morbidity and mortality resulting from hypoxemia. A standard therapy for obstructive sleep apnea is nasal continuous positive airway pressure (CPAP). D'Ambrosio and colleagues performed a prospective study to evaluate the effect of CPAP on quality of life in persons with obstructive sleep apnea.
The study included 23 men and six women referred to a university sleep laboratory for evaluation of sleep-disordered breathing. Those diagnosed with obstructive sleep apnea who did not have any other sleep disorders and had not received any treatments other than CPAP were included in the study. At baseline, all study subjects completed a Medical Outcomes Study Short Form-36 (SF-36), a survey tool that measures how patients perceive their own functional status, well-being and overall health. Questions are included to measure whether certain life or social activities have stopped or decreased as a result of health or emotional problems.
After the optimal amount of CPAP was established for each patient, therapy was maintained for eight weeks. At the end of eight weeks, the patients again completed the SF-36 assessment form.
The average age of the subjects was 44 years, with a range of 23 to 68 years. Many of the patients had comorbid illnesses, including heart disease, diabetes mellitus and hypertension, but all were stable at the time of initial evaluation and at follow-up. All of the study subjects had markedly low SF-36 scores compared with age-matched control subjects. The study subjects had severe obstructive sleep apnea with an average respiratory disturbance index of 77 events per hour, an arousal index of 67 arousals per hour and an arterial oxygen desaturation level that decreased from 94.1 percent while awake to 79.0 percent during sleep.
After eight weeks of CPAP for an average of six hours per night, the respiratory disturbance index decreased to four events per hour and the arousal index decreased to 13 arousals per hour. The mean oxygen saturation during sleep increased to 91.6 percent. All of the patients reported significant increases in vitality, social functioning and mental health compared with baseline. No correlation was apparent between the severity of the obstructive sleep apnea, respiratory disturbance index scores or oxygen saturation and improvement in SF-36 scores. However, patients with lower scores before treatment demonstrated greater improvement after treatment.
The authors conclude that patients with obstructive sleep apnea have marked impairments in all aspects of quality of life, including emotional and physical health, as well as social functioning. The use of CPAP can result in significant improvements in these areas. This improvement appears to occur regardless of the severity of the respiratory dysfunction.
JEFFREY T. KIRCHNER, D.O.
D'Ambrosio CD, et al. Quality of life in patients with obstructive sleep apnea. Effect of nasal continuous positive airway pressure--a prospective study. Chest January 1999;115:123-9.
How Should Physicians Counsel Patients About Cannabis Use?
Many young adults in developed countries report a history of experimentation with cannabis. Approximately 10 percent of those who try cannabis become daily users, and an additional 20 to 30 percent use the drug weekly over prolonged periods. These patterns of usage are of concern because of the adverse health effects associated with heavy cannabis use, and the associated use of alcohol, tobacco and other drugs. Hall and Solowij review the current literature on the adverse health effects of acute and chronic use of cannabis.
The principal psychoactive compound in cannabis is d-9-tetrahydrocannabinol (THC). Marijuana contains between 0.5 and 5 percent THC and hashish contains between 2 and 20 percent. Cannabis is usually smoked, because users can maximize THC absorption in the lungs by inhaling deeply and holding their breath. Immediate effects include euphoria and relaxation, intense sensory perceptions and time distortion. Other effects include talkativeness, impaired motor skills and dysfunction in attention and short-term memory. Ingestion of cannabis elevates both heart rate and blood pressure, but these findings are considered negligible in healthy young adults, as tolerance to these cardiovascular effects develops. The most unpleasant side effects are anxiety and panic reactions, and these are often cited by users as reasons for discontinuing the drug. To date, cannabis poisoning has not resulted in any confirmed deaths. The most serious consequence of cannabis use may be that of driving while impaired. However, studies on the effects of cannabis use on driving performance have been equivocal.
Chronic use of cannabis affects multiple body systems, specifically the respiratory, immune and reproductive systems. Heavy cannabis smoking increases the symptoms associated with chronic bronchitis, a problem that appears to be independent of, but synergistic with, the effects of tobacco. Histopathologic changes that precede lung cancer and cancers of the aerodigestive tract have been reported in young adults who are heavy users. Animal studies indicate that cannabis smoke may be carcinogenic, both directly and through its adverse effects on the immune system, but these findings may be uncertain since the doses of THC used in these studies were very high. Other animal studies show that THC decreases testosterone production and generally impairs fertility in both males and females; however, these results have not been replicated in humans. Cannabis use in pregnancy does not seem to increase the risk of birth defects; however, birth weight seems to be lower, and children exposed to cannabis in utero appear to have behavior and development difficulties, especially in attention, memory and higher cognitive functioning. These children also appear to have an increased risk of developing certain types of cancer and leukemia.
Chronic use is also associated with subtle impairments of higher cognitive functions, such as memory and attention. Prolonged use of cannabis leads to a dependence syndrome similar to that of alcohol, affecting approximately one in 10 users. In adolescents, heavy cannabis use is associated with academic underachievement, job instability, problems in family relationships, involvement in crime and use of other illicit substances.
The authors conclude that there is increasing evidence of adverse health effects associated with cannabis use. They emphasize that much remains to be understood about its long-term effects on humans. Studies of cannabis users are complicated by the co-existence of other variables, especially alcohol use and other behavior risk factors. Patients should be advised about the possible health hazards of cannabis use, particularly the risks associated with driving when cannabis is combined with alcohol or other illicit substances.
ANNE D. WALLING, M.D.
Hall W, Solowij N. Adverse effects of cannabis. Lancet November 14, 1998;352:1611-6.
Acupuncture for Treatment of Back Pain: A Meta-Analysis
Survey data indicate that back pain is one of the most common reasons for referral to acupuncturists. Even though several plausible mechanisms may explain the efficacy of treatment with acupuncture, reviews of published data on the benefits of using acupuncture are inconclusive. Ernst and White performed a meta-analysis of randomized, controlled trials that evaluated acupuncture in the treatment of back pain.
The adequacy of the acupuncture therapies cited was assessed by six consulting acupuncturists. Although 12 studies were available for analysis, only nine provided suitable data, according to strict criteria that included outcome measures. There was no heterogeneity among the studies and the expert acupuncturists held divergent opinions about the adequacy of the treatments in nearly all the studies.
A total of 377 patients with chronic back pain or those who had failed to respond to conventional therapy had been recruited for the studies. Only two studies excluded patients with previous back surgery. Thus, the majority of patients were associated with a poor prognosis, and treatment would have been considered a challenge at best. In three studies, the outcome was markedly more positive than in the other studies. The lack of uniformity in the inclusion criteria, acupuncture approach, setting and end points could not account for the divergence of the data. Collectively, these data suggested that acupuncture is an effective treatment for back pain. The fact that the overall result is positive suggests that acupuncture can be helpful even in difficult cases of chronic back pain.
The authors conclude that the combined results of the studies show acupuncture to be superior to various control interventions. The analysis of the literature in this area included only randomized, controlled trials, thus lending weight to the findings. Results of this meta-analysis reveal the complexity of defining efficacy in studies of alternative medicine.
BARBARA APGAR, M.D., M.S.
Ernst E, White AR. Acupuncture for back pain. A meta-analysis of randomized controlled trials. Arch Intern Med November 9, 1998;158:2235-41.
EDITOR'S NOTE: Previous surveys have indicated that 15 percent of smokers would use alternative therapies to give up smoking. In another article in this issue, a randomized trial on the use of acupuncture to reduce nicotine withdrawal symptoms included 66 adults who desired to stop smoking. Results indicated that there was no significant difference in the mean reduction of withdrawal symptoms from day 1 to day 14. The effects of acupuncture were entirely nonspecific, suggesting that acupuncture is a powerful placebo for smoking cessation. Acupuncture appeared to have little value in preventing relapse and should be used in conjunction with other smoking aids to effect a positive response.
B.A.
Infant Circumcision and Risk of Urinary Tract Infection
Neonatal circumcision remains a controversial procedure when it is performed for reasons other than religious belief. Among the medical benefits cited is a reduction in urinary tract infections (UTIs) in infant boys following circumcision. To and colleagues studied Canadian boys from birth to three years of age to assess the relationship between UTIs and circumcision.
All singleton boys born to residents of Ontario during 1993, excluding those who were circumcised after the first month of life, were included in the study. Of the 69,100 boys, 30,105 (43.6 percent) were circumcised and 38,995 were uncircumcised. No infant had signs of urinary tract infection before the procedure.
The boys were followed for three years, during which time 83 circumcised boys and 247 uncircumcised boys were admitted to a hospital for UTI. Over 90 percent of these infants were admitted only once for UTI. The cumulative rate of hospital admissions for UTI was 1.88 per 1,000 in circumcised boys and 7.02 per 1,000 in uncircumcised boys by the end of the first year. The comparable figures at three years were 2.96 for circumcised boys and 8.75 for uncircumcised boys. The authors calculate the relative risk of hospital admission for uncircumcised boys as 3.0 during the first year of life. When data from outpatient billings for UTI in boys younger than three years were included in the calculations, the relative risk of UTI in uncircumcised boys fell to 1.73.
The authors conclude that previous studies have overestimated the risk of UTI in uncircumcised male infants. Although the rate of UTI is slightly increased in uncircumcised boys, UTI is rare, occurring in less than 1 percent of boys under one year of age. Approximately 195 circumcisions would need to be performed to prevent one hospital admission for UTI.
ANNE D. WALLING, M.D.
To T, et al. Cohort study on circumcision of newborn boys and subsequent risk of urinary-tract infection. Lancet December 5, 1998;352:1813-6.
Do 'Health Products' Really Help Athletic Performance?
Both creatine, a natural amino acid derivative, and androstenedione, a testosterone precursor, are marketed and sold as "dietary supplements." Widely believed to enhance athletic performance, these products received national attention following the record-breaking home-run performance of baseball player Mark McGwire, who reportedly takes both. Neither supplement is labeled by the U.S. Food and Drug Administration for any indication. Consultants from The Medical Letter reviewed the available data.
Creatine is naturally present in food sources such as meat and fish. Cells with high energy requirements use creatine in the form of phosphocreatine, which serves as a phosphate donor to generate adenosine triphosphate (ATP) from adenosine diphosphate. There is enough phosphocreatine and ATP in skeletal muscle cells for about 10 seconds of high-intensity activity. In one short-term study, the use of creatine supplements increased body mass primarily because of increased water retention. A 28-day placebo-controlled trial that studied eight weightlifters found that taking 20 g per day of creatine produced a significant increase in strength, body weight and fat-free mass. A summary of 31 studies of short, high-intensity tasks suggested that oral creatine supplements modestly improved performance. However, most of these studies were performed in the laboratory. In actual field trials, no benefit was demonstrated. Other studies failed to show a consistent advantage to creatine use during aerobic activity.
Oral creatine appears to be well tolerated with no adverse effects reported in healthy men who used recommended dosages. Creatine supplements are not banned by athletic organizations such as the International Olympic Committee (IOC) and the National Collegiate Athletic Association (NCAA).
Androstenedione is available in the United States in tablet form, often in combination with other steroids. By itself, androstenedione has little intrinsic activity, although it is a direct precursor of estrone and testosterone. Taking supraphysiologic dosages of testosterone has been shown to increase nitrogen retention and muscle strength and mass. Whether these same effects are achieved with the use of androstenedione is unknown. There are few published studies on the effects of androstenedione use. One study demonstrated a four- to sixfold increase in the levels of blood testosterone within one hour of ingesting 100 mg of androstenedione.
Long-term data on the safety of androstenedione are not available. Adverse effects from the use of exogenous testosterone in men are well known and include acne, testicular atrophy and behavioral changes. In women, adverse effects include hirsutism, male-pattern baldness, amenorrhea and clitoral hypertrophy. Adolescents who take exogenous testosterone may experience early closure of the bone growth plates and decreased adult height. Many athletic organizations, including the IOC, NCAA and National Football League, ban the use of androstenedione.
The Medical Letter consultants concluded that although creatine supplements may modestly improve athletic performance in some brief, high-intensity activities in laboratory settings, the benefits have not been documented in actual on-field activities. Although androstenedione can increase the levels of blood testosterone, the effect it has on muscle mass remains to be established. Currently, it is assumed that androstenedione produces the same adverse effects as exogenous testosterone. The potency and purity of both creatine and androstenedione supplements in the U.S. market are currently unknown.
BARBARA APGAR, M.D., M.S.
Medical Letter consultants. Creatine and androstenedione--two 'dietary supplements.' Med Lett Drug Ther November 6, 1998;40(1039):105-6.
Prophylactic Mastectomy to Prevent Breast Cancer
Prophylactic mastectomy of women at high risk of developing breast cancer has been available as one method of prevention for many years. However, little data have documented the effectiveness of this aggressive approach. Hartmann and colleagues at the Mayo Clinic conducted a retrospective analysis of women who had undergone prophylactic mastectomy at their institution over a 33-year period.
The medical records for women who had undergone prophylactic mastectomy from 1960 to 1993 were identified from the surgical index recording system at the Mayo Clinic. The starting date of 1960 was selected because it was soon after this time that breast implants became available, allowing for postmastectomy reconstruction. A total of 1,065 women underwent mastectomy during this period, and 639 of these women had a documented family history of breast cancer. This cohort of women was then divided into high-risk and moderate-risk groups. High-risk criteria included features suggestive of an autosomal dominant predisposition to breast cancer. These criteria included: two or more first-degree relatives with breast cancer; one first-degree relative plus two or more second- or third-degree relatives with breast cancer; one first-degree relative with breast cancer before age 45 and one other relative with breast cancer; one first-degree relative with bilateral breast cancer; or three or more second- or third-degree relatives with breast cancer. Three other "high-risk" groups included the criteria of ovarian cancer because of the established relationship between these two diseases.
The authors used the Gail model to predict the expected incidence of breast cancer in these women. This model is based on data from 243,221 white women who underwent annual screening for breast cancer for five years. The calculations with the Gail model include specific clinical information such as age at menarche, age of first live birth, number of previous breast biopsies and presence of a first-degree relative with breast cancer.
The women with a family history of breast cancer included 214 women in the high-risk group and 425 women in the moderate-risk group. The median age of mastectomy in all women was 42 years, with a range of 18 to 79 years. The median length of follow-up was 14 years, and the minimum follow-up was two years. Of these women, 609 (95 percent) were alive at the time the data were reviewed. Six women were found to have an incidental breast cancer at the time of prophylactic surgery. Breast cancer occurred in seven women after the surgery, with six cases confined to the chest wall at diagnosis. Among the moderate-risk group, the predicted number of breast cancers over a 14-year period was 37 cases, while the actual incidence was only four. The calculated incidence of expected number of deaths in the moderate-risk group was 10.4 cases, and the actual number was zero. In the high-risk group, the predicted incidence of death ranged from 10.5 to 30.6, depending on how the calculations were performed. The actual number of deaths in the high-risk group was only two.
The authors conclude that prophylactic mastectomy lowers the risk of breast cancer and the risk of dying from the disease. The decision to undergo this surgical procedure must be weighed against other factors, including the need for breast reconstruction, the effect on a woman's body image, the irreversibility of the procedure and the knowledge that breast cancer may never develop.
JEFFREY T. KIRCHNER, D.O.
Hartmann LC, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med January 14, 1999;340:77-84.
Allergic Rhinitis: Intranasal Steroids or Antihistamines?
Allergic rhinitis is a common condition that appears to be increasing dramatically in prevalence. Besides local symptoms, rhinitis can cause fatigue, diminish work performance and quality of life, and predispose patients to sinusitis and otitis. The two principal treatment strategies are intranasal corticosteroids and systemic antihistamines (H1-receptor antagonists) but, despite multiple studies, the choice of therapy is often arbitrary. Weiner and colleagues conducted a meta-analysis of randomized, controlled trials to compare the efficacy of antihistamines and intranasal corticosteroids in the management of allergic rhinitis.
Searches of literature databases and contact with researchers identified 16 trials that met the study's criteria for quality. These trials included 2,267 patients and generally assessed the effect of therapy on nasal blockage, itch, discharge, sneezing, postnasal drip and general nasal discomfort.
Apart from one study in which oral therapy was shown to provide better relief of sneezing, intranasal steroids provided significantly greater relief of symptoms in all categories in every study. No significant difference was found between the two therapies in relief of eye symptoms.
The authors conclude that despite methodologic differences between the studies, the finding that intranasal steroids provide superior symptomatic relief in allergic rhinitis is remarkably consistent. No evidence of severe adverse effects have been found even after five years of continuous use. Steroids also were more cost effective than oral antihistamines as first-line therapy. The authors propose that oral antihistamines may be best used as ancillary therapy, particularly in patients with eye symptoms.
ANNE D. WALLING, M.D.
Weiner JM, et al. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ December 12, 1998;317:1624-9.
Cessation of Breast Feeding in Infants with Atopic Eczema
Breast feeding is considered beneficial in infants with atopic tendencies because human milk confers immunologic protection at the intestinal surface. This protection may continue beyond infancy. Yet allergy may develop in infants who are exclusively breast-fed, perhaps because they have become sensitized to dietary antigens in their mother's milk or because of the absence of some vital immunoregulatory components in the milk. Another possibility is that infants become sensitized by inhalation or direct allergen contact. Because of contradictory findings from previous studies of early sensitization and breast feeding, Isolauri and associates evaluated whether breast feeding should or should not continue in infants with atopic eczema.
Included in the study were 100 exclusively breast-fed infants with moderate or severe atopic eczema. The infants ranged in age from two weeks to six months (mean age: two months) when atopic eczema initially developed. Growth, nutrition and the extent of allergic sensitization were evaluated during and after breast feeding. In addition, the infants' mothers completed a questionnaire on their perceptions of their infants' symptoms. A family history of atopic disorders was verified in 77 of the patients. On the emergence of atopic eczema, all of the mothers modified their diets; 80 eliminated basic foods such as milk and milk products, eggs and fish, and 20 eliminated single foods such as citrus fruits.
Scores reflecting the severity of atopic eczema were higher during breast feeding than after breast feeding ceased. Fifty-nine of the infants were found to have cow's milk allergy. During breast feeding, the infants' growth was less than what would be expected for age during breast feeding, even though the amount of milk intake was not different from what would be expected. An association was found between the duration of symptoms and poor growth. With cessation of breast feeding, normal growth and nutritional parameters were restored, suggesting that sustained food allergy may cause poor growth in infants. Elimination diets undertaken by the mother did not produce a reversal in the sensitization that had already developed into allergic disease. Symptoms of atopic eczema decreased with cessation of breast feeding.
The authors conclude that there may be a delicate balance between immunoprotection and inflammatory response in breast-fed allergic infants. Breast feeding may maintain allergic symptoms in sensitized infants, which may impair their growth. In such infants, breast feeding should perhaps be stopped.
RICHARD SADOVSKY, M.D.
Isolauri E, et al. Breast-feeding of allergic infants. J Pediatr January 1999;134:27-32.
"Tips from Other Journals" are written by the medical editors of American Family Physician.
Copyright © 1999 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.
