 |
||
|
Articles | Departments
| |
||
Tips from Other Journals
Benefit of Theophylline on COPD-Related Erythrocytosis
Patients with chronic obstructive pulmonary disease (COPD) tend to develop erythrocytosis to compensate for the chronic hypoxic state. This compensatory mechanism may result in increased blood viscosity, requiring extended oxygen therapy and repeated phlebotomies. Theophylline is effective in reducing hematocrit and erythropoietin levels in patients with erythrocytosis following renal transplantation. Oren and associates retrospectively and prospectively evaluated the possibility that theophylline would be beneficial in modifying erythrocytosis in patients with COPD.
In the retrospective study, hematocrit levels were found to be significantly lower in the 50 patients receiving theophylline, compared with the levels in the 61 patients not receiving this drug. Since oxygen saturation was similar in both groups, the normal hematocrit levels in the theophylline group could not be entirely explained by improved oxygen availability alone.
In the prospective study, arterial oxygen saturation did not significantly increase during theophylline therapy. However, hematocrit levels declined significantly in seven of eight patients after three months of theophylline therapy. The greatest response was observed in the three most severely polycythemic patients. Serum erythropoietin levels declined by 21 to 91 percent in five of the seven patients in whom this variable was studied. The most significant decrease in the erythropoietin level occurred in the patient with the most severe polycythemia. Of four patients who discontinued theophylline therapy after three months, three had increased hematocrit levels within one month of stopping the medication.
The authors believe that, although the side effects of theophylline may limit its use in some patients, the possible beneficial effects demonstrated in this study may outweigh the side effects. They encourage the use of theophylline in patients with COPD-related erythrocytosis.
BARBARA APGAR, M.D., M.S.
Oren R, et al. Effect of theophylline on erythrocytosis in chronic obstructive pulmonary disease. Arch Intern Med 1997;157:1474-8.
Calcium Supplementation and Prevention of Preeclampsia
Preeclampsia, usually defined as the onset of hypertension and proteinuria in the second half of pregnancy, occurs in about 5 percent of pregnancies. The pathophysiology of preeclampsia is not well understood, and the search for an effective preventive therapy has been unsuccessful. The results of several clinical trials and meta-analyses of these studies have suggested that calcium supplementation may help prevent preeclampsia. Levine and colleagues report on the results of the Calcium for Preeclampsia Prevention (CPEP) trial, a study sponsored by the National Institutes of Health and conducted at five medical centers.
The CPEP trial enrolled a cohort of 4,589 women. Almost 12,000 nulliparous women who were in their 11th to 21st week of pregnancy were screened for possible inclusion. Patients were excluded if they were receiving any prescribed medications, had an elevated baseline serum creatinine or calcium level or had a history of renal disease (including calculi) or hematuria.
Women who were initially determined to be eligible for the study were given a single-blind test of compliance for six to 14 days. Study subjects were considered compliant if they took at least 75 percent of placebo tablets. The patients were divided into two groups. Members of the treatment group were given tablets containing 500 mg of calcium carbonate and were asked to take two tablets with their morning and evening meals until delivery. The placebo group received tablets containing cornstarch and sugar and were given identical instructions. Follow-up visits were conducted every four weeks until the 29th week of pregnancy, every two weeks through the 35th week and weekly thereafter until delivery. Standardized measurements of blood pressure and urinary protein excretion were performed at each prenatal visit.
A total of 2,295 women received calcium and 2,294 received placebo. White, Hispanic and African-American women were equally represented in each group. Twelve percent of the patients from each group were current cigarette smokers. The number of prenatal visits, unscheduled outpatient visits and prenatal hospitalizations was the same in both groups. The average compliance with medication was 64 percent in the calcium group and 67 percent in the placebo group.
The incidence of preeclampsia was 6.9 percent in the calcium group and 7.3 percent in the placebo group. In women with preeclampsia, no difference in gestational age at the time of the diagnosis was noted between the calcium group and the placebo group. No statistically significant differences were apparent between the two groups in the incidence of pregnancy-associated hypertension without preeclampsia, pregnancy-associated proteinuria without hypertension and all other hypertensive disorders. The mean systolic blood pressure was slightly but not significantly lower in the calcium group than in the placebo group, although the calcium group had a slightly higher diastolic pressure.
The rate of obstetric complications, including cesarean section, placental abruption and urolithiasis, did not differ between the two groups. No significant difference was apparent between the calcium and placebo groups in the rate of preterm deliveries or perinatal deaths.
The authors conclude that prenatal supplementation with 2 g of calcium daily in nulliparous women does not reduce the incidence or severity of preeclampsia, nor does it delay the onset of preeclampsia. In addition, calcium does not reduce the incidence of pregnancy-associated hypertension. It also does not appear to affect the incidence of cesarean delivery, preterm delivery or perinatal death, as was suggested by previous studies.
JEFFREY T. KIRCHNER, D.O.
Levine RJ, et al. Trial of calcium to prevent preeclampsia. N Eng J Med 1997;337:69-76.
Cytology of Fluid from Nonpalpable Breast Masses
Differentiating a cyst from a solid lesion of the breast by ultrasonography may be difficult, especially if the cyst contains mildly echogenic proteinaceous debris. Routine cytologic examination of fluid from breast cysts is recommended by some authorities, while others believe it is not useful. Most authors, however, advocate cytologic analysis if the fluid is bloody. Previous studies of the utility of cytologic analysis of fluid from breast cysts have been performed in women with palpable breast masses. Smith and associates studied the utility of cytologic examination of fluid from nonpalpable breast masses with the sonographic appearance of simple cysts.
The results of cytologic examination in 583 women (660 nonpalpable breast cysts) evaluated over 42 months were retrospectively reviewed. The fluid was obtained by sonographically or mammographically guided needle aspiration.
No malignant cells were seen on cytologic examination of fluid from 541 cysts (82 percent of the cysts). Insufficient material was obtained from 86 cysts (13 percent of the cysts). In 33 cysts (5 percent), atypical cells were identified on cytologic examination. Surgical biopsy was performed in nine of these patients; histology revealed fibrocystic changes in eight patients and intraductal papilloma in one patient. The remaining 24 patients received periodic follow-up examinations, and all of the lesions appeared smaller or were not seen during the follow-up examination.
Grossly bloody fluid was obtained from 42 cysts. Three exhibited a dark color, suggesting old blood, but no atypical cells were noted on cytologic examination. Of the remaining 39 cysts with bloody fluid, five showed atypical cells on cytologic examination. Four of these five patients underwent biopsy, and all results were benign.
The authors conclude that if the fluid obtained from radiologically guided aspiration of nonpalpable breast cysts is not bloody, routine cytologic examination is not necessary unless other radiologic findings suggest malignancy. The authors recommend that grossly bloody fluid be sent for cytologic analysis, although the yield appears to be low.
BARBARA APGAR, M.D., M.S.
Smith DN, et al. Impalpable breast cysts: utility of cytologic examination of fluid obtained with radiologically guided aspiration. Radiology 1997;204:149-51.
Childhood Spanking and Increased Antisocial Behavior
About 90 percent of parents use some form of corporal punishment on toddlers, and about 50 percent continue to use it during the early teen years, despite a growing body of evidence that it does not positively affect a child's behavior and may actually result in increased aggressive or delinquent behaviors. Straus and colleagues examined the relationship between corporal punishment and antisocial behavior in children.
A sample of 807 mothers with children between the ages of six and nine years was drawn from an original cohort of women who were part of the National Longitudinal Survey of Youth-Child Supplement conducted at Ohio State University. The mothers completed an antisocial behavior (ASB) scale that described their child's behavior over the preceding three months. Descriptive items in the ASB scale included the following: "cheats or tells lies," "bullies or is cruel or mean to others," "does not feel sorry after misbehaving," "breaks things deliberately," "is disobedient at school" and "has trouble getting along with teachers." The items were scored as "often true," "sometimes true" and "not true."
Categories ranging from no spanking in the past week to spanking 15 or more times in the past week were used to assess the frequency of spanking. For the purpose of statistical analysis, the numbers were broken into four categories of how many times the child was spanked in one week: zero (451 children), one time (160), two times (114) and three or more times (82). Using the ASB scale, data were collected at baseline and again two years later. The study was controlled for several independent variables, including sex, race, socioeconomic status, cognitive stimulation and parental emotional support.
Spanking was significantly related to the ASB score at baseline and two years later. In the zero-frequency spanking group, the ASB score actually declined four points from baseline. In contrast, the ASB score increased 14 points in the group of children whose mothers reported spanking them three or more times at baseline. The consistent finding was that the more frequent the spanking at the beginning of the study, the greater the ASB scores two years later. The trend toward increased ASB scores was stronger in boys than in girls and also in American children of European descent compared with minority children. The tendency also persisted regardless of the extent to which parents provided cognitive stimulation and emotional support to their children.
The authors conclude that corporal punishment or spanking is a statistically significant predictor of subsequent antisocial behavior, even in children who may be spanked only once a week. They believe their data show a "dose response" to corporal punishment, starting with young children. The more frequently spanking is used, the longer its negative effects last and the greater the likelihood that it will induce behavior problems. They further suggest that reducing or completely eliminating corporal punishment would be beneficial to society, since antisocial behavior is associated with violence and more serious crimes committed by teenagers and adults.
JEFFREY T. KIRCHNER, D.O.
Straus MA, et al. Spanking by parents and subsequent antisocial behavior of children. Arch Pediatr Adolesc Med 1997;151:761-7.
Magnetic Fields and Risk of Childhood Leukemia
Studies linking residential exposure to magnetic fields from power lines with an increased risk of childhood cancers have produced conflicting results, and their epidemiologic methods have been questioned. This inconsistency has led to uncertainty and public concern about the relationship between residential exposure to magnetic fields and the occurrence of childhood leukemia. Linet and associates evaluated this relationship in a study of children under the age of 15 years with acute lymphoblastic leukemia who were registered with the Children's Cancer Group.
The study evaluated 638 children with acute lymphoblastic leukemia and matched them with 620 control subjects. Exposure to magnetic fields generated by nearby power lines was measured. Obtaining historic data was important in tracking exposure, so mothers of the study subjects and the control subjects were asked to provide lifetime residential histories for the children. Magnetic fields were measured in homes in which the children had lived for at least six months and usually within 24 months of the diagnosis of acute lymphoblastic leukemia in affected children. Exposure was calculated as the average of the summary level for the eligible measured home, weighted by the amount of time in the residence. Four exposure categories were identified, ranging from less than 0.065 µT to 0.200 µT or more.
The relationship between power line configuration and the strength of the magnetic field varies geographically. Therefore, residential wire-code categories were used to evaluate pairs of children with acute lymphoblastic leukemia and control subjects. Measured magnetic fields increase with increasing wire-code categories. For each child, one or two homes were measured, provided that the child had lived in one of them for at least 70 percent of the reference period. Twelve of the 428 pairs of children were excluded because technicians could not locate homes or accurately diagram nearby power lines. Homes were also evaluated if mothers had lived there during at least five months of the pregnancy that produced the child with leukemia.
The authors found there was no significant excess risk of childhood acute lymphoblastic leukemia at residential magnetic field levels of 0.200 µT or greater. No significant dose-response trends were identified. There was no association with high wire codes for either the child's main residence or the mother's residence during pregnancy.
The authors conclude that data from this study do not support an increased risk of acute lymphoblastic leukemia associated with residential magnetic field exposure up to 0.200 µT. They note that there is little support for the hypothesis that high levels of residential exposure or living in homes close to electric power lines is related to childhood acute lymphoblastic leukemia.
KATHRYN M. ANDOLSEK, M.D., M.P.H.
Linet MS, et al. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 1997;337:1-7.
Diagnosis, Treatment and Prevention of Giardiasis
Giardiasis has become an increasingly common cause of diarrhea and malabsorption in humans. Thirty-four outbreaks of giardiasis were reported in the United States from 1993 to 1994, compared with just six outbreaks in 1984. Ortega and Adam review the epidemiology and life cycle of Giardia and discuss current treatment and prevention.
Giardia lamblia is most often transmitted through contaminated water or food, or by the fecal-oral route. Outbreaks peak in late summer, except in day care centers, where no seasonal patterns have been observed. G. lamblia occurs throughout the world and is most prevalent in areas with poor water treatment or unsanitary conditions. The seroprevalence in developing countries ranges from 20 to 30 percent. Most of these persons are asymptomatic. A seroprevalence rate as high as 35 percent has been reported in children attending day care centers. Although many of these children are asymptomatic, they may transmit the infection to family members.
The usual incubation period for symptomatic giardiasis is one to two weeks but may vary from one to 45 days. However, as many as 60 percent of persons exposed to the infection remain asymptomatic. Patients who develop symptoms usually have loose diarrhea with foul-smelling, non-bloody stools. Other common symptoms include flatulence, abdominal cramps, bloating, anorexia, nausea and weight loss. Fever sometimes occurs at the onset of infection. Malabsorption is common and is the likely cause of the substantial weight loss that may occur. Unlike those with other forms of infectious diarrhea, patients with giardiasis will usually be symptomatic for one to two weeks before seeking medical attention. The illness may resolve spontaneously, but symptoms may persist for weeks and sometimes for months. Chronic infection occurs despite the presence of an antibody-mediated immune response. The reasons for this are unclear; however, the antibodies do seem to provide protection against newly acquired infection or reinfection.
The diagnosis of giardiasis is usually confirmed by the presence of cysts or, less frequently, trophozoites in stool specimens stained with trichome or iron hematoxylin. The sensitivity of this test can be improved by repeating the stool examination on one or two additional specimens. Giardia antigens can be detected in stool specimens using monoclonal antibodies or direct fluorescent assays. These tests should be considered if the results of routine stool examinations are nondiagnostic. Serodiagnosis is not useful because current antibody tests are unable to differentiate between present and prior infection.
In patients with persistent symptoms, a string test may be useful. In this test, the patient swallows a capsule on the end of a string which migrates to the jejunum, where the trophozoites attach. The string is withdrawn after four hours or more and can then be examined for trophozoites. Some clinicians prefer to proceed to esophagogastroduodenoscopy with duodenal aspiration and biopsy. This method aids in the detection of other diseases that may cause similar symptoms, such as lymphoma, Whipple's disease, cryptosporidiosis, isosporiasis or Crohn's disease.
Several effective treatments are currently available for patients with symptomatic giardiasis (see the accompanying table). The majority of patients will respond to a five-day course of metronidazole. Quinacrine hydrochloride had been considered the drug of choice for giardiasis but, due to the side effects of hemolysis and toxic psychosis in some patients with glucose-6 phosphate dehydrogenase deficiency, it is no longer commercially available in the United States. Tinidazole, given as a single dose, is widely used throughout the world but is not labeled for this use by the U.S. Food and Drug Administration. Furazolidone is currently the only drug labeled for the treatment of giardiasis in the United States and is often used to treat children. Albendazole seems to be comparable to metronidazole in efficacy and has fewer side effects. Paromomycin is a nonabsorbable aminoglycoside that is not as effective as the other available agents but is commonly used for the treatment of giardiasis in pregnant women.
Effective Drugs in the Treatment of Giardiasis Drug Dosage
Metronidazole 250 mg three times per day for five days (15 mg per kg per day) Quinacrine 100 mg three times per day for five days (6 mg per kg per day) Furazolidone 100 mg four times per day for seven to 10 days (6 to 8 mg per kg per day) Paromomycin 25 to 30 mg per kg per day in three doses for seven days Albendazole 400 mg per day for five days Tinidazole 2 g (in a single dose)
Reprinted with permission from Ortega YR, Adam RD. Giardia: overview and update. Clin Infect Dis 1997;25:545-50.The prevention of infection with G. lamblia should focus primarily on the avoidance of contaminated water. Vigorous hand-washing and proper disposal of soiled diapers should be practiced in day care settings. Outbreaks of giardiasis have usually been associated with contaminated surface water or shallow wells. The most effective method of rendering Giardia cysts nonviable is boiling the water. Chlorination is not effective. Filtration with a pore size of 2 µm or smaller is also effective for removing Giardia cysts from water.
JEFFREY T. KIRCHNER, D.O.
Ortega YR, Adam RD. Giardia: overview and update. Clin Infect Dis 1997;25:545-50.
Characteristics and Symptoms in Patients with Autism
In the United States, autism may affect up to 115,000 children between one and 15 years of age, but its prevalence in adults is uncertain. Classic autism is one of a group of development disorders in which a wide variety of behaviors and activities are demonstrated that collectively are known as pervasive development disorder (see the accompanying table on criteria for autistic disorder). Certain biologic conditions and/or genetic factors appear to be associated with the development of autism, but no specific cause has been identified. Multiple members of a family may be affected, but currently no common genetic defect is observable in affected children. Rapin reviewed the many manifestations of autism, principal symptoms, therapies and prognosis.
Criteria for Autistic Disorder* A total of six or more manifestations from 1, 2 and 3 below:
- Qualitative impairment of social interaction (at least two manifestations)
- Marked impairment in the use of multiple types of nonverbal behavior such as eye-to-eye gaze, facial expression, body postures and gestures to regulate social interactions;
- Failure to develop peer relationships appropriate to development level;
- Lack of spontaneous seeking to share enjoyment, interests or achievements with other people (e.g., by lack of showing, bringing or pointing out objects of interest); and
- Lack of social or emotional reciprocity.
- Qualitative impairment of communication (at least one manifestation)
- Delay in, or lack of, development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gestures or mime);
- In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others;
- Stereotyped and repetitive use of language or idiosyncratic language; and
- Lack of varied, spontaneous make-believe play or social imitative play appropriate to development level.
- Restrictive and stereotyped patterns of behavior, interests and activities (at least one behavior manifestation)
- Encompassing preoccupation with one or more restricted, repetitive and stereotyped patterns of interest that is abnormal either in intensity or focus;
- Apparently inflexible adherence to specific, nonfunctional routines or rituals;
- Stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements); and
- Persistent preoccupation with parts of objects.
- Delays or abnormal functioning, with onset before the age of three years, in at least one of the following areas:
- Social interaction;
- Language as used in social communication; and
- Symbolic or imaginative play.
- A determination that Rett's disorder or childhood disintegrative disorder does not account better for the observed symptoms.
*--Adapted from DSM-IV.
Reprinted with permission from Rapin I. Autism. N Engl J Med 1997;337:97-104.
Autism can first appear as impaired attachment in infants, but this behavior generally occurs in toddlers, typically in boys from 18 to 30 months of age. They may demonstrate affection but without any joy or reciprocity. In these children, parents also report delayed speech, lack of normal interest in others or in childhood activities, or a regression of early speech and sociability.
Communication difficulties are the most serious problem. Patients with verbal auditory agnosia ("word deafness") understand little or no language (see accompanying table on communication deficits in autism). In addition, children with autism do not play normally. While they may appear to have long attention spans when engaged in solitary activities, they cannot focus on activities performed jointly with others. Parents may describe them as independent rather than aloof and may even be proud of their self-sufficiency. Children with autism have frequent temper tantrums, require less sleep and awaken frequently during the night. Approximately 75 percent of children with autism are mentally retarded, but a small minority excel at music, mathematics or visual spatial tasks.
Communication Deficits in Autism Aspect of language Deficits
Phonology (speech sounds) Impaired reception and expression in children with the mixed receptive-expressive syndrome and, especially, with severe verbal auditory agnosia (word deafness) in which phonologic decoding may be so compromised as to preclude speech comprehension and verbal expression Prosody (rhythm and melody of speech) In children with speech: singsong or rising intonation, high-pitched voice or monotonous, "robotic" speech Syntax (grammar and word order) Impaired reception and expression in children with the mixed receptive-expressive syndrome and with less severe verbal auditory agnosia Semantics (vocabulary and meaning of language) Impaired reception and expression in all children with autism--e.g., impaired comprehension of questions, open-ended questions and nonliteral language such as irony, sarcasm and jokes; word-retrieval problems and unusual, pedantic word choices; echolalia; difficulty formulating coherent discourse; narrow range of topics Pragmatics (communicative and conversational use of language) Impaired reception and expression in all persons with autism--e.g., impaired interpretation of tone of voice, body posture and facial expression; gaze avoidance; failure to answer; speaking to no one in particular; failure to initiate, pursue or terminate conversations; difficulty with taking turns; poor maintenance of topic; perseveration and ceaseless questioning
Reprinted with permission from Rapin I. Autism. N Engl J Med 1997;337:97-104.Neurologic problems associated with autism include joint laxity, hypotonia, clumsiness, apraxia, toe walking, motor stereotypies (such as hand flapping, pacing, spinning, running in circles) and oral stereotypies (such as humming). Self-destructive behavior such as biting and head banging may be the result of increased endorphin levels. These children may be either hypersensitive or oblivious to sounds, tactile stimuli, pain and tastes. As adolescents, they frequently demonstrate detachment, depression and unprovoked aggression.
The functional status of persons with autism varies widely. They may not function well enough to perform activities of daily living or, alternatively, they may successfully complete college and function independently. In well-functioning adults, stereotypies, such as finger rubbing, may persist unnoticed. However, by the time a child with autism reaches adulthood, he or she has likely had at least two seizures. In addition, autism in adults may be confused with other diagnoses such as obsessive-compulsive disorder, schizoid personality, simple schizophrenia, affective disorder, mental retardation or brain damage.
Mainstream treatment consists of early, intensive education for parents, focusing on behavior and communication disorders. A highly structured environment with intensive individual instruction should be encouraged. Laboratory, metabolic or genetic tests and diagnostic imaging provide little useful information, although an electroencephalogram (EEG) is indicated in children in whom epilepsy is suspected. No specific pharmacologic therapies are available, but many patients do not require medication. When needed, medication is generally used for a particular manifestation or constellation of symptoms. Families may benefit from ongoing counseling and support, and specific instructions for dealing with tantrums and destructive behavior. Parents should be cautioned about costly and often questionable dietary, medical and other unconventional therapies.
KATHRYN M. ANDOLSEK, M.D., M.P.H.
Rapin I. Autism. N Engl J Med 1997;337:97-104.
Ultrasonographic Dating for Down Syndrome Screening
Prenatal screening results for Down syndrome and fetal open neural tube defects are subject to substantial variation depending on the gestational age of the fetus at the time screening tests are performed. For open neural tube identification, ultrasonographic evaluation of gestational age by biparietal diameter measurement alone should be advantageous. Use of ultrasonographic dating for Down syndrome screening should increase the detection rate. Benn and associates conducted a study to determine whether gestational age should be based on ultrasonographic evaluation or on the last menstrual period in the interpretation of second-trimester maternal serum screening for Down syndrome and open neural tube defects.
The study included 24,000 pregnant women who underwent triple testing (maternal serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol) at 15.0 to 21.9 weeks of gestation. When dating by ultrasonographic evaluation and dating by last menstrual period were available before testing, the ultrasonographic data were used for gestational age assessment and test interpretation. Sixty percent of the test interpretations were based on ultrasonographic evaluation of gestational age. In 24 Down syndrome pregnancies, dating by ultrasonography and dating by last menstrual period were both available at the time of the screening. The proportion of patients who initially screened positive for Down syndrome was 5.02 percent for women with gestational age determined by ultrasound and 9.33 percent for women with gestational age determined by the last menstrual period. This represented a significant difference.
After age adjustment, the screen-positive rate for the ultrasonography group was still significantly different from the rate for the last menstrual period group. The detection rate for Down syndrome was higher when ultrasonographic dating was used than when last menstrual period was used (76 versus 60 percent). Fourteen of the 24 cases of Down syndrome had a higher risk for Down syndrome when dating from the last menstrual period was used. Dating using the last menstrual period gave a gestational age 5.3 days older than the gestational age obtained by ultrasound. Using these data, the odds of having a fetus with Down syndrome given a positive triple test was one in 63 when dating was based on the last menstrual period and one in 37 when dating was based on ultrasound.
The rate of women who initially screened positive for open neural tube defects and also screened positive on revised testing was significantly higher when gestational age was based on ultrasonographic dating than when dating was based on the last menstrual period.
The authors conclude that screening for Down syndrome appears to be almost twofold more efficient using ultrasonographic dating. Imprecision associated with dating from the last menstrual period resulted in a substantial number of post-test ultrasonographic evaluations, recalculations and retestings. The number of anmiocenteses recommended for the ultrasonography group was significantly less than that for the group dated by the last menstrual period. Although the authors do not recommend routine ultrasonographic examination for women undergoing triple testing, they do suggest that when ultrasonographic information is available, it should be preferentially used over data from the last menstrual period because it significantly improves the effectiveness of triple testing.
BARBARA APGAR, M.D., M.S.
Benn PA, et al. Down syndrome and neural tube defect screening: the value of using gestational age by ultrasonography. Am J Obstet Gynecol 1997;176:1056-61.
Ceftriaxone vs. Doxycycline for Disseminated Lyme Disease
Accurate diagnosis of Lyme disease and the appropriate selection of therapy are critical for a good outcome. Borrelia burgdorferi, the causative spirochete, may disseminate to organs and the central nervous system early in the course of infection. Such patients appear clinically more ill than those who present with a history of a tick bite and the rash of erythema migrans. It is unclear, however, whether patients with systemic symptoms should be treated with an oral antibiotic or with parenteral ceftriaxone. Dattwyler and colleagues compared the effectiveness and tolerability of parenteral ceftriaxone and oral doxycycline in 140 patients with acute disseminated Lyme disease but without meningitis.
Patients eight years of age and older who had been in an area where Lyme disease was endemic and who had at least one expanding annular lesion 5 cm or greater in diameter were included in the open-label, randomized trial. Lyme disease was considered disseminated if at least one of the following was present: more than one erythema migrans lesion, carditis manifested by heart block, acute large-joint arthritis and neurologic abnormalities (including seventh-cranial-nerve palsy or radiculitis of less than three months' duration). The diagnosis of Lyme disease was serologically confirmed by enzyme-linked immunosorbent assay and Western blot testing.
Patients were randomly assigned to receive either ceftriaxone, 2 g intravenously or intramuscularly daily for two weeks, or doxycycline, 100 mg orally twice daily for 21 days. The dosages in children were 50 mg per kg of ceftriaxone (up to 2 g daily) and 4.4 mg per kg of doxycyline (up to 100 mg twice daily).
A total of 68 patients received ceftriaxone, and 72 received doxycycline. Sixty-two study subjects in the ceftriaxone group and 71 in the doxycycline group had multiple erythema migrans lesions. The mean duration of the rash before treatment was nine days in the ceftriaxone group and 10 days in the doxycycline group. Patients were seen weekly during treatment and at three, six and nine months after completion of antibiotic therapy. At each follow-up visit the investigators classified the patient's clinical response as a "cure" (resolution of objective clinical findings of Lyme disease) or "treatment failure" (persistence of clinical findings, including arthritis and neurologic disease).
By the end of the study, 85 percent of the ceftriaxone group and 88 percent of the doxycycline group were cured. Treatment failure was noted in only one patient from each group, although assessment could not be performed in nine patients from the parenteral group and eight patients from the oral therapy group. Not surprisingly, 57 percent of the ceftriaxone group reported at least one adverse drug event, compared with 43 percent of the doxycycline group. Eighteen of 67 patients (27 percent) in the ceftriaxone group reported residual symptoms at the final evaluation; 14 had arthralgia and six reported fatigue. In contrast, 10 of 71 patients (14 percent) in the doxycycline group reported residual symptoms at the final evaluation; six had arthralgia and five reported fatigue.
The authors conclude that oral doxycycline should continue to be the first line of treatment for acute disseminated Lyme disease. Use of ceftriaxone should be reserved for patients with Lyme meningitis or for patients in whom tetracycline or penicillin is contraindicated.
In a related article, Eckman and colleagues performed a cost and quality-of-life analysis of data from multiple studies (including the Dattwyler study) that compared oral doxycycline with parenteral ceftriaxone in the treatment of Lyme disease. They concluded that intravenous ceftriaxone is no more effective than oral doxycycline, causes more complications and is substantially more expensive. The evidence is quite firm that oral therapy is appropriate in the majority of patients with Lyme disease.
JEFFREY T. KIRCHNER, D.O.
Dattwyler RJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med 1997;337:289-94, and Eckman MH, et al. Cost effectiveness of oral as compared with intravenous antibiotic therapy for patients with early Lyme disease or Lyme arthritis. N Engl J Med 1997;337:357-63.
Effect of Chlorthalidone on Prevention of Heart Failure
Isolated systolic hypertension frequently precedes heart failure. The Systolic Hypertension in the Elderly Program (SHEP) showed that low-dose chlorthalidone significantly reduced the incidence of stroke and major cardiovascular events. Kostis and colleagues, for the SHEP Cooperative Research Group, evaluated the effect of diuretics on the occurrence of heart failure in study patients with isolated systolic hypertension.
Patients were randomized to receive either placebo or 12.5 mg per day of chlorthalidone. If this dosage did not satisfactorily control blood pressure within two months, it was increased to 25 mg per day. If this, too, failed to lower blood pressure, atenolol in a dosage of 25 mg per day or matching placebo was added. A final increase to 50 mg of atenolol daily or matching placebo was allowed, if needed. Patients began open-label treatment if the stepped-care protocol did not control their hypertension. Heart failure was diagnosed if patients had dyspnea at rest, orthopnea or paroxysmal nocturnal dyspnea, or were in New York Heart classification III. Also, one or more of the following signs was required: rales, 2+ ankle edema, tachycardia of greater than 120 beats per minute, radiographic evidence of cardiomegaly or congestive heart failure, S3 gallop or distention of the jugular vein.
A total of 2,365 patients were randomized to receive active treatment, and 2,371 received placebo. At baseline, only 0.3 percent of the patients had a history of heart failure. Five years after baseline, 90 percent of the patients were receiving some form of antihypertensive therapy. Heart failure (both fatal and nonfatal) was less prevalent in the treatment group than in the placebo group. During an average of 4.5 years of follow-up, fatal and nonfatal heart failure occurred in 55 of the 2,365 patients receiving therapy and in 105 of the 2,371 patients receiving placebo (relative risk: 0.51). The risk of heart failure was greater in those with higher systolic blood pressures at baseline and in those who were older. Patients receiving active therapy in each higher-risk group had a lower rate of heart failure than patients in the placebo group with these risk factors. The addition of atenolol was not found to provide any additional protection from heart failure compared with chlorthalidone alone.
The authors conclude that diuretic-based stepped-care treatment of isolated systolic hypertension in the elderly is protective against the development of heart failure in this population. The reduction in risk of heart failure is approximately 50 percent and, in patients with a history of myocardial infarction, the reduction may range up to 80 percent.
GRACE BROOKE HUFFMAN, M.D.
Kostis JB, et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1997;278:212-6.
Steroid-Sparing Effect of Methotrexate in Asthma
Airway inflammation is a key component in the pathogenesis of asthma. Consequently, anti-inflammatory therapies, primarily corticosteroids, are the cornerstone of therapy for patients with severe asthma. Alternative anti-inflammatory therapies, including methotrexate, have been evaluated in numerous studies, but the results have been discrepant. Marin performed a meta-analysis of 11 studies published between 1988 and 1996 to determine whether low-dose methotrexate decreased the amount of steroids needed to maintain clinical stability in adults with steroid-dependent asthma. He also attempted to determine whether the steroid-sparing effect of methotrexate was related to the vigor with which steroids were tapered and whether methotrexate therapy improved pulmonary function.
Ninety articles were reviewed, and 11 were ultimately included in the meta-analysis. These studies included a total of 199 patients. All patients had received therapy with prednisone or methylprednisolone in varying dosages. The majority of the studies examined short-term use of methotrexate (three to four months). Three studies evaluated methotrexate therapy for six months or longer. With one exception, the methotrexate dosage was 15 mg per week.
In six studies, methotrexate was not found to have a steroid-sparing effect, but in five studies it was associated with a decrease in the steroid dosage of an average of 4.37 mg per day (23.7 percent of the initial dosage). The average steroid dosage for all of the studies pooled together was 8.24 mg per day, and the average dosage at initiation of the protocols was 18.40 mg per day. Six of the studies included a "run-in" period in which the steroid dosage was first reduced to the lowest level needed for clinical stability. None of the 11 studies reported an improvement in pulmonary function based on forced expiratory volume in one second (FEV1). No life-threatening side effects or serious adverse events resulting from methotrexate therapy were reported in any of the studies.
The author concludes that low-dose methotrexate has a statistically significant steroid-sparing effect in patients with steroid-dependent asthma. Efficacy is most pronounced in patients who receive methotrexate for 24 weeks. Therapy should not be started until the patient is taking the lowest possible dose of oral steroids.
In an accompanying editorial, Mullarkey cites data supporting the use of methotrexate early in the course of the asthma, similar to its use in the treatment of rheumatologic and dermatologic conditions. He believes that the risk-benefit profile clearly favors methotrexate over prednisone. His usual prescribing practice is to reduce the steroid dosage to the lowest effective level, begin methotrexate therapy, and then continue it for six months after the patient has been fully weaned from prednisone. Patients should continue to receive their usual asthma medication. He calls for additional controlled studies of methotrexate in chronic asthma as well as the development of additional steroid-sparing drugs.
JEFFREY T. KIRCHNER, D.O.
Marin MG. Low-dose methotrexate spares steroid usage in steroid-dependent asthmatic patients. Chest 1997;112: 29-33, and Mullarkey MF. Methotrexate revisited [Editorial]. Chest 1997;112:1-3.
Diagnosis and Treatment of Depression in the Elderly
In 1991, the National Institutes of Health issued a consensus statement about the diagnosis and treatment of depression in the elderly. Lebowitz and associates reviewed the conclusions of this statement in light of recent findings.
Depression that first occurs in late life is more likely to have a chronic course and is more likely to occur in women. In elderly patients, depression with cognitive impairment that improves with antidepressant treatment is also a predictor of irreversible dementia. Newer research is supporting the high prevalence rates (13 to 27 percent) of "subsyndromal" depression--that is, the presence of depressive symptoms that do not meet diagnostic criteria for major depression as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). In the long-term care population, subsyndromal depression may exist in as many as one half of the residents.
The reasons to diagnose and treat depression in the elderly are many: to hasten symptom remission, to prevent relapse, to improve the patient's quality of life, to improve functional status and to prevent premature death. Newer antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs), have been compared with the older tricyclic antidepressants and have been found to be more effective. Both medications are beneficial in 60 to 80 percent of patients, but the SSRIs are associated with higher levels of tolerance, fewer dosage adjustments and greater acceptance among the elderly. Psychotherapy, in various forms, has also been shown to be efficacious in treating late-life depression. It may be especially useful in patients who cannot or will not take antidepressant medication. Treatment for late-life depression should continue for at least six months beyond recovery for patients with first-onset depression and for at least one year beyond recovery for those with recurrent depression. Some patients with recurrent depression may need lifelong treatment with antidepressants.
Suicide rates in elderly persons increased 9 percent between 1980 and 1992. Primary care physicians are less likely to be told by their patients about suicidal intent than psychiatrists, so it is particularly important for primary care physicians to be aware of the symptoms of depression (other than just mood disturbance) and to ask about suicidal ideation in patients with those symptoms. One important clue in the detection of depression is a complaint of a persistent sleep disturbance.
The authors conclude that, with vigilance, primary care physicians can recognize, diagnose and treat depression in the elderly in order to improve quality of life and maintain function at the highest levels possible.
GRACE BROOKE HUFFMAN, M.D.
Lebowitz BD, et al. Diagnosis and treatment of depression in late life. Consensus statement update. JAMA 1997; 278:1186-90.
Eliminating LDH Tests in Acute Myocardial Infarction
Although hospital protocols vary in regard to the work-up of suspected myocardial infarction, most include tests for creatine kinase (CK), with or without lactate dehydrogenase (LDH), to rule out myocardial infarction. With the introduction of CK isoenzyme MB (CK-MB) measurements, LDH isoenzyme testing has been shown to have a minimal role in excluding myocardial infarction in patients with chest pain of less than 24 hours' duration. Randall and Jones evaluated the institutional impact of eliminating LDH testing from their hospital's cardiac protocol and surveyed 100 U.S. hospitals to determine which tests are routinely performed to rule out myocardial infarction.
There was no report of harm to a patient during the 12 months after LDH testing was removed from the routine cardiac enzyme protocol. Of the 200 patients with one or more abnormal cardiac enzyme levels, none had positive LDH results and negative CK-MB results. No patients had a diagnosis of acute myocardial infarction on the basis of the LDH isoenzyme results.
In the year before elimination of LDH testing from the protocol, 6,177 LDH isoenzyme tests were ordered. The total annual cost was more than $47,000 at this hospital. In the intervention year, only 14 LDH isoenzyme tests were ordered, costing $154. All yielded negative results. Removal of LDH isoenzyme testing from the protocol cut the expenditure for this test by more than 99 percent.
Despite data showing little benefit of routine LDH isoenzyme testing and national consensus recommendations that this testing be abandoned, the authors' nationwide survey of 100 hospitals revealed that two thirds of the hospitals continue to use such testing in their cardiac protocols. Of the 66 hospitals that require routine LDH testing on the day of admission, 12 percent have it ordered every six to 12 hours, 55 percent every eight hours and 33 percent daily.
The authors conclude that routine LDH isoenzyme testing is unnecessary in patients who present within the first 24 hours of a possible acute myocardial infarction. Guidelines endorsed by organizations such as the American Heart Association recommend that levels of LDH and LDH isoenzymes be determined only in patients with negative results on CK tests and chest pain of more than 24 hours' duration. The authors also propose that elimination of LDH tests in this setting is likely to be well accepted and to yield substantial institutional savings.
BARBARA APGAR, M.D., M.S.
Randall DC, Jones DL. Eliminating unnecessary lactate dehydrogenase testing: a utilization review study and national survey. Arch Intern Med 1997;157:1441-4.
Screening for Depression: Two Questions to Ask Patients
Screening for depression can be problematic, since most screening instruments are long and time-consuming. The main features of depression, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), are a two-week history of depressed mood and loss of interest in most activities. Whooley and colleagues evaluated a two-question instrument to determine its adequacy in identifying patients with major depression.
The two questions asked were as follows: (1) "During the past month, have you often been bothered by feeling down, depressed or hopeless?" and (2) "During the past month, have you often been bothered by little interest or pleasure in doing things?" The results of this two-question test were compared with those of other tests that have been substantiated to screen for depression.
Patients attending an urgent care clinic were asked to participate in the study. A self-report questionnaire and a structured interview were administered. Demographic information and any history of depression were obtained in each patient. The two questions were then asked. Subsequently, the other six validated tests were administered. A blinded review of medical records was conducted to determine whether the physician who saw the patient recognized depression in the patient.
A total of 536 patients participated in the study. The prevalence of major depression in this patient population was 18.1 percent, as determined by the National Institute of Mental Health Diagnostic Interview Schedule (a structured interview based on DSM-IV criteria). The physicians identified depression in only 8.8 percent of the patients. The two-question test had a sensitivity of 96 percent and a negative predictive value of 98 percent. The positive predictive value was 33 percent. The two-question test found 17 true positives and one false negative for every 100 patients tested.
The authors conclude that this two-question screening tool for depression is as effective as other instruments in detecting depression. If a patient answers "no" to both questions, he or she is very unlikely to have depression.
GRACE BROOKE HUFFMAN, M.D.
Whooley MA, et al. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med 1997;12:439-45.
EDITOR'S NOTE: Other studies have shown similar findings, namely that extensive instruments for depression screening may be no more effective, and certainly are more cumbersome, than simply asking a patient if he or she is or has been feeling depressed or sad. The standard instruments still have a role in identification of patients who are depressed, but a simpler test may be better in the case of screening for depression.--g.b.h.
Nocturnal Hypoglycemia in Children with Type 1 Diabetes
Intensive insulin therapy delays the onset of diabetic complications but increases the risk of severe hypoglycemia. In children with type 1 (insulin-dependent) diabetes, hypoglycemia may impair normal brain development and neurophysiologic function. Tight glycemic control in children with diabetes requires extreme caution. About one half of the severe hypoglycemic episodes in children occur during the night, when self-monitoring of blood glucose levels is unlikely. Asymptomatic nocturnal hypoglycemia may cause loss of perception of neurogenic hypoglycemia symptoms, predisposing children to severe hypoglycemia. Beregszàszi and associates evaluated the prevalence of nocturnal hypoglycemia in 150 children with type 1 diabetes.
Patients in the study were under age 16 and had had type 1 diabetes for more than one year. Most of them were receiving conventional twice-daily insulin mixtures, and a small proportion were receiving more intensive therapy by means of three or more daily insulin injections. The study participants were admitted to the hospital, and blood samples were obtained hourly through a catheter for 22 hours starting at 10 p.m. Nurses recorded manifestations of hypoglycemia, such as sweating, tremor and agitation.
The overall prevalence of at least one hypoglycemic event during the 22-hour period of monitoring was 46.7 percent (70 patients). Hypoglycemia was asymptomatic in nearly one half of the children. In 48 of the 70 patients with nocturnal hypoglycemia (68 percent), the initial hypoglycemic episode occurred between 10 p.m. and midnight. Multiple episodes of hypoglycemia were noted in seven patients. The proportion of children reporting at least one hypoglycemic episode during the daytime on the day before admission was significantly higher in the group with nocturnal hypoglycemia (31 percent versus 16 percent in children without nocturnal hypoglycemia), as was the percentage of patients in whom urinary C-peptide was undetectable.
The findings suggest that the risk of nocturnal hypoglycemia is higher in children than in adults with type 1 diabetes. Hypoglycemia began most frequently three to five hours after the evening insulin injection. This is understandable in view of the pharmacokinetics of a mixture of short- and intermediate-acting insulins. Previous studies have shown that risk factors for nocturnal hypoglycemia include lower hemoglobin A1c levels, a longer duration of diabetes and higher insulin dosages.
Four additional risk factors for nocturnal hypoglycemia in children were identified: younger age, the occurrence of two or more episodes of severe hypoglycemia after the onset of diabetes, more than one episode of hypoglycemia weekly for the preceding month, and daily insulin dosages exceeding 0.85 IU per kg. The authors found that a blood glucose threshold of 93.6 mg per dL (5.2 mmol per L) or less before dinner is highly predictive of the occurrence of subsequent nocturnal hypoglycemia.
The authors note that a snack at around 10 p.m. for all children cannot be advocated, because their study was not designed to test this approach. They state that their data suggest that a snack at 10 p.m. for all children could worsen nocturnal hyperglycemia. Further studies are needed to evaluate potential advantages of a snack at 10 p.m.
RICHARD SADOVSKY, M.D.
Beregszàszi M, et al. Nocturnal hypoglycemia in children and adolescents with insulin-dependent diabetes mellitus: prevalence and risk factors. J Pediatr 1997;131:27-33.
Accelerated vs. Conventional Radiotherapy for Lung Cancer
Three quarters of all cases of lung cancer are due to nonsmall-cell lung cancer (NSCLC). Conventional radiotherapy usually involves administration of 2 Gy five times a week, to a total dosage of 60 Gy over a six-week period in the hope of balancing tumor treatment and damage to surrounding normal tissue. Saunders and colleagues studied the efficacy and safety of radiotherapy given as three daily treatments of 1.5 Gy for 12 consecutive days in patients with locally advanced NSCLC.
British patients with inoperable NSCLC who met criteria for radical radiotherapy were included in the study. Of 563 patients, 225 were randomized to receive conventional radiotherapy and 338 were randomized to receive accelerated therapy, called continuous hyperfractionated accelerated radiotherapy (CHART). With CHART, the duration of radiotherapy was reduced from 40 days to 12 days with the intent of minimizing the opportunity for cell proliferation.
Patients were followed weekly for six weeks, and then at eight weeks and three months after the first day of radiotherapy. For the next two years, follow-up was every three months, after which a follow-up visit was conducted every six months. Follow-up studies included chest radiographs and computed tomography performed every six months, as well as assessment of symptoms, particularly dysphagia.
In the conventional treatment group, 40 patients (18 percent) did not complete treatment as planned. In the CHART group, 29 (9 percent) did not complete therapy. The 13 participating centers began enrolling patients in 1990, and since that time 444 study participants have died. The one-year survival rate was 63 percent in patients treated with CHART, compared with 55 percent in the group receiving conventional radiotherapy. The survival rate at two years was 29 percent for patients treated with CHART and 20 percent for patients treated with conventional radiotherapy. Analysis of subgroups suggested that CHART may be most effective in patients with squamous cell carcinoma.
CHART patients reported more severe problems with dysphagia during treatment. In the CHART group, 19 percent were able to swallow only fluids, compared with 3 percent of the conventional radiotherapy group. Dysphagia resolved at three months in most patients, although 9 percent of the CHART patients and 7 percent of the conventionally treated patients reported persistent dysphagia. The degree of dysphagia reported usually was slight.
Radiation pneumonitis was slightly more common in the conventional radiotherapy group. In this group, 65 percent had radiologic changes, and 19 percent were symptomatic. In the CHART group, 56 percent had radiologic changes, and 10 percent had symptoms of radiation pneumonitis.
The authors conclude that CHART provided significant improvement in survival in patients with NSCLC, particularly in patients with squamous cell carcinoma. CHART was associated with a higher percentage of patients who completed therapy. Although initial radiation-induced symptoms were more severe in CHART patients, they resolved more rapidly in these patients than in patients treated conventionally.
ANNE D. WALLING, M.D.
Saunders M, et al. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in nonsmall-cell lung cancer: a randomised multicentre trial. Lancet 1997;350:161-5.
Sexual Transmission of Hepatitis C Virus
Although sexual transmission of hepatitis C virus (HCV) has not been definitively established, the strongest evidence for this route of transmission comes from epidemiologic studies of non-A, non-B hepatitis. Studies of the prevalence of antibodies to HCV (anti-HCV) among persons who are at risk for this disease have been conflicting. Thus, no recommendations have been made about immune globulin prophylaxis for sexual partners of infected persons. Piazza and associates studied the risk of sexual transmission of HCV and evaluated the efficacy of immune globulin prophylaxis in preventing transmission of the infection to sexual partners.
The randomized, controlled trial included 899 heterosexual partners of persons positive for anti-HCV; 64.3 percent of the partners were women. The partners were randomized to receive 4 mL of immune serum globulin, prepared from unscreened donors, or placebo, every two months. Tests for HCV infection were performed every four months. A total of 884 subjects completed the study.
Seven sexual partners (four women and three men) developed HCV infection as documented by test results positive for HCV RNA. Six persons were in the placebo group and one was in the prophylaxis group. The risk of acquiring HCV infection was significantly higher in the control group. In untreated partners, the relative risk of becoming positive for HCV RNA was 10.7. None of the members of the placebo group who became infected had been exposed to any parenteral risk factors.
Anti-HCV and HCV RNA tests were conducted every six months during follow-up of partners who became infected. Follow-up ranged from 20 to 24 months. All of the infected partners had persistent viremia. Two persons became symptomatic. After 20 months, four of the seven infected partners underwent liver biopsy, which revealed chronic active hepatitis. Sequence homology studies strongly suggested sexual transmission of HCV.
The authors conclude that these study results demonstrate that HCV can be sexually transmitted. HCV transmission occurred only in the partners of HCV-infected patients with active liver disease. The sexual partners who acquired HCV infection during the study tended to be older (54 years versus 43 years) and tended to have a longer sexual relationship (27 years versus 18 years) with the infected person. Until the introduction of a vaccine for HCV, the authors believe that immune globulin prophylaxis may afford significant protection against sexual transmission of HCV.
BARBARA APGAR, M.D., M.S.
Piazza M, et al. Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin: a randomized controlled trial. Arch Intern Med 1997;157:1537-44.
Safety of Tetracycline, Minocycline and Doxycycline
Minocycline has been reported to cause rare life-threatening events, such as hypersensitivity syndrome reaction, serum sicknesslike reaction and drug-induced lupus erythematosus. A review of the Drug Safety Clinic database (from 1985 through 1996), the Health Protection Branch data (from 1966 through October 1996) and MEDLINE (from 1966 to October 1996) was conducted to determine whether similar events are associated with the use of tetracycline and doxycycline. Shapiro and associates reported on the specific events surrounding use of the tetracycline antibiotics and also reported on cases of isolated single-organ dysfunction.
Based on available reports, more serious adverse events resulted from minocycline use than from use of the other tetracycline antibiotics. The reports emphasized the importance of recognizing early and late complications of tetracycline antibiotics. Early complications included cases of hypersensitivity syndrome reaction, serum sicknesslike reaction and isolated single-organ dysfunction that occurred within two months of treatment. Symptoms included fever, malaise and arthralgia with or without major organ involvement. Late reactions include drug-induced lupus, which occurs on average two years after therapy is started but can occur up to six years after therapy is started.
A total of 86 percent of the hypersensitivity syndrome reactions were attributed to minocycline. Isolated single-organ dysfunction attributable to tetracycline and doxycycline manifests most commonly as a severe cutaneous adverse reaction, whereas single-organ dysfunction related to minocycline most commonly manifests as pneumonitis. The association of minocycline with drug-induced lupus appears to be most common in young women. No cases of either tetracycline- or doxycycline-induced lupus were reported. Minocycline is the least frequently prescribed of the three tetracycline drugs, but it has the largest fraction of repeat prescriptions. This situation reflects the pattern of long-term use in the treatment of acne vulgaris and may also help explain the sole association of minocycline with drug-induced lupus.
Risk management strategies for administering tetracyclines should include pretreatment identification of risk factors, communication of potential adverse events and management of complications in a expeditious manner. Since minocycline is clearly associated with drug-induced lupus, its use should be avoided in patients with systemic lupus or those who have a first-degree relative with a history of lupus. Appropriate investigations of an early reaction include a complete blood cell count, determination of hepatic enzyme levels, a urinalysis and kidney function tests, a chest radiograph and thyroid function tests three months after the acute event. It is recommended that patients with a tetracycline-induced hypersensitivity syndrome reaction and their first-degree relatives avoid tetracycline antibiotics altogether.
In late reactions, tests for antinuclear antibody and hepatic enzymes are appropriate. It does not appear to be necessary to routinely monitor patients receiving long-term minocycline therapy, such as adolescents receiving oral tetracycline or minocycline for acne.
The authors conclude that because of the severity of tetracycline-related adverse events, patients who experience a serious adverse event while taking one of the tetracycline antibiotics should be advised to avoid all tetracyclines in the future.
BARBARA APGAR, M.D., M.S.
Shapiro LE, et al. Comparative safety of tetracycline, minocycline, and doxycycline. Arch Dermatol 1997;133: 1224-30.
Cryptococcal Meningitis in Patients with AIDS
Cryptococcal meningitis can be a life-threatening fungal infection in patients who are positive for human immunodeficiency virus (HIV) infection. In the past, the treatment of choice was amphotericin B and flucytosine, but flucytosine has had toxic effects in patients with acquired immunodeficiency syndrome. Newer oral triazole antifungal drugs, such as fluconazole and itraconazole, have been developed as alternatives to the traditional therapies. Van der Horst and colleagues studied the effectiveness of different combinations of antifungal medications in patients with a first episode of AIDS-associated cryptococcal meningitis.
In phase one of the study, 381 patients were given amphotericin B combined with flucytosine or placebo. Phase two consisted of consolidation therapy with either fluconazole or itraconazole. After two weeks, cerebrospinal fluid cultures were negative in 202 patients (60 percent) who received amphotericin B with flucytosine and in 179 patients (51 percent) who received amphotericin B alone. The clinical status of the two groups was similar. At this time, 306 patients were considered stable or improved and judged eligible for the second phase of the study. In phase two of the study, 151 patients were given fluconazole and 155 received itraconazole for an additional eight weeks.
At the conclusion of phase two, cultures of cerebrospinal fluid were negative in 72 percent of the patients treated with fluconazole and in 60 percent of the patients treated with itraconazole. However, cultures were not obtained in 39 patients in the fluconazole group and in 54 patients in the itraconazole group. Sixty-eight percent of patients treated with fluconazole and 70 percent of patients treated with itraconazole were asymptomatic after phase two. Similar percentages in both groups had unchanged or improved scores on the Mini-Mental State Examination.
The authors recommend that initial treatment of AIDS-associated cryptococcal meningitis consist of higher-dose amphotericin B in combination with flucytosine for two weeks, followed by eight weeks of fluconazole. The addition of flucytosine to amphotericin B during the first two weeks of therapy, followed by treatment with fluconazole for the next eight weeks, was independently associated with cerebrospinal fluid sterilization and may prevent relapse. In this study, the addition of lower-than-typical doses of flucytosine to amphotericin B for the first two weeks of treatment did not increase the efficacy of treatment or the incidence of toxic effects. Itraconazole is a suitable alternative for patients who are unable to tolerate fluconazole.
KATHRYN M. ANDOLSEK, M.D., M.P.H.
van der Horst CM, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. New Engl J Med 1997;337:15-21.
Withdrawal of Medication for High Blood Pressure
Medications used to treat hypertension are known to reduce the risk of complications such as stroke, congestive heart failure, renal failure and myocardial infarction that are often associated with hypertension. Despite strong evidence of the effectiveness of such medications, little is known about whether they should be continued throughout a patient's lifetime. Withdrawal of medications has far-reaching implications, including reductions in potentially serious side effects and savings to patients that may range up to $1 billion annually. Froom and colleagues reviewed available studies of the withdrawal of antihypertensive medications and surveyed 1,000 family physicians in New York state regarding the frequency of such attempts.
An extensive MEDLINE search yielded only 18 trials in which antihypertensive medications were withdrawn from patients. Despite differences in research design and patient characteristics, data from 12 trials were combined for use and judged appropriate for reporting in this study. Four of the 12 trials used placebo, and six studies were limited to patients 60 years of age and older. Successful withdrawal was achieved in 40.3 percent of 765 patients at one year; at two years, only 27.7 percent of patients were still not taking the medication. In patients 60 years of age and older, successful withdrawal was achieved in 26.2 percent for an average period of two years or more. All trials displayed decreasing success rates over time.
A number of factors predicted the success of withdrawal. The most common predictor was a lower blood pressure before treatment. Other factors included female gender, lower diastolic blood pressure during treatment, absence of family history of hypertension, ease of control of blood pressure with medication, and both longer and shorter duration of therapy. In addition, combining weight reduction and a decreased salt and alcohol intake with medication withdrawal was more successful than withdrawal of medication alone.
Of the 1,000 family physicians surveyed about attempts to withdraw antihypertensive therapy in patients, 535 responded. Among these, 79 percent reported that they sometimes stopped therapy in patients whose blood pressure was well controlled and who were free of symptoms. On average, these physicians had discontinued antihypertensive medications in 5.6 patients in the preceding six months. These results suggest that a substantial percentage of family physicians in New York state attempt to withdraw medications in some of their patients.
The authors support previously reported recommendations that withdrawal may be attempted in patients taking a single antihypertensive agent who are normotensive for six to 12 months, and those taking a single agent for mildly elevated blood pressure if they have lost weight and/or begun to exercise during therapy. Once medication is withdrawn, patients should be monitored every three to six months for the rest of their lives and should be encouraged to maintain proper weight, to exercise and to avoid excess intake of sodium and alcohol. Patients taking multiple blood pressure medications may be candidates for withdrawal of all but one medication after achieving normotensive status for six to 12 months. Counseling for risk factor reduction should be provided.
KATHRYN M. ANDOLSEK, M.D., M.P.H.
Froom J, et al. Withdrawal of antihypertensive medications. J Am Board Fam Pract 1997;10:249-58.
Treatment of Cytomegalovirus Retinitis in AIDS Patients
Cytomegalovirus disease affects up to 44 percent of patients with acquired immunodeficiency syndrome, generally when the patient's CD4 count is less than 50 per mm3. Eighty-five percent of patients with cytomegalovirus disease associated with AIDS develop retinitis. Symptoms include blurring vision, loss of central vision, scotomata, floaters and photopsia, depending on the site of retinal involvement. Destroyed retinal areas do not regain function, so the goal of treatment is to prevent further retinal involvement that could lead to additional visual symptoms. Recurrence is common, and retinal detachment occurs in 25 percent of patients given antiviral therapy. Jacobson reviewed four new therapies that have been reported in the last three years for the treatment of AIDS-related cytomegalovirus retinitis.
Ganciclovir, foscarnet and cidofovir are currently used for treatment of cytomegalovirus retinitis. In clinical trials, intravenous ganciclovir and foscarnet have been shown to be equally effective. However, neutropenia and thrombocytopenia often develop in patients using ganciclovir, limiting the dosage. With both drugs, daily intravenous treatments are required for the rest of the patient's life. Oral ganciclovir is less effective than the intravenous agent and can only be used when the retinitis is not located near the fovea.
Intraocular implants containing ganciclovir release the drug for up to eight months at higher retinal concentrations than that obtained with standard intravenous therapy. The implant procedure may cause transient visual loss that typically resolves within a few weeks. Only 10 percent of patients develop more significant adverse events that compromise vision as a result of the procedure. Since implants have virtually no systemic effect against cytomegalovirus, retinitis often manifests in the other eye. In addition, gastrointestinal, neurologic or pulmonary cytomegalovirus disease often develops in patients with implants.
Cidofovir is 10 to 100 times more potent than the other drugs and its effect is prolonged, so intermittent intravenous administration is possible. However, its complications include irreversible nephrotoxic effects through proximal tubular cell injury, neutropenia, peripheral neuropathy, low intraocular pressure, anterior uveitis and alopecia.
Most patients with cytomegalovirus retinitis experience relapse despite prolonged therapy with antiviral medications. Switching from ganciclovir to foscarnet may benefit patients whose retinitis is rapidly progressive despite treatment with high-dose intravenous ganciclovir. However, routinely switching from one drug to another at the time of a relapse is not necessarily more effective than continuing high-dose therapy with the initial drug.
Another treatment strategy involves using standard doses of combined intravenous ganciclovir and foscarnet, since the combination may be twice as effective in delaying disease progression as high doses of either drug given alone. However, more patients experience drug intolerance with the combined regimen, resulting in discontinuation of the combination. In addition, uncontrolled studies of twice-weekly intravitreal injections with either ganciclovir or foscarnet have shown that the progression of retinitis has stopped, with little morbidity. Trials are currently in development to test the combination of cidofovir and ganciclovir.
The author concludes that choosing among the available treatment options involves balancing efficacy, toxic effects, adverse outcomes and patient lifestyle preferences. Newer agents are currently undergoing clinical trials.
KATHRYN M. ANDOLSEK, M.D., M.P.H.
Jacobson MA. Treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. N Engl J Med 1997;337:105-14.
Antibiotic Utilization in Hospitalized Elderly Patients
It has been estimated that from 25 to 33 percent of hospitalized patients receive antibiotics and that in 22 to 65 percent of cases, these antibiotics are inappropriately or incorrectly prescribed. Fraser and associates developed a case-oriented educational approach to changing the prescribing behavior of clinicians and conducted a prospective randomized trial to evaluate the clinical, microbiologic and economic effectiveness of this intervention.
Elderly hospitalized patients receiving one or more of 10 designated parenteral antibiotics for three or more consecutive days over a three-month period were identified through pharmacy records and included in the study. A total of 252 patients were randomized to either an intervention group (141 patients) or a control group (111 patients). The intervention group received antibiotic-related suggestions from a team consisting of a pharmacist and an infectious disease specialist. These suggestions were placed in the medical progress note section of the patient's medical record. The groups were subsequently compared to determine the effectiveness of this intervention.
A total of 74 suggestions were made for 62 patients in the intervention group. Approximately 63 (85 percent) of the suggestions were implemented, with the majority (75 percent) involving changes in antibiotic choice, dosing regimen or route of administration. Evaluative disagreements between the investigators were uncommon and primarily involved assessing the status of patients to determine if they were stable enough to attempt changes in antibiotic treatment. There were no disagreements regarding antibiotic choice, route of administration, dosage or duration of treatment.
Assessment of the economic benefit of implementing suggestions resulted in significantly fewer intravenous antibiotics being prescribed, reducing the number of hospital days required. Patients in the intervention group spent 1.6 fewer days taking parenteral antibiotics. The less intensive intravenous antibiotic treatment in the intervention group also reflected a trend toward lower defined daily dosages per patient treatment course. Eighty percent of patients in both groups showed clinical improvement. The intervention group required less retreatment with antibiotics (defined as the need for readministration of antibiotics within seven days) and a shorter duration of hospitalization.
Randomization to the intervention group was found to be a significant predictor of reduced charges for antibiotic therapy. The intervention blended three strategies successfully: it was initiated by opinion leaders in infectious disease, it offered patient-specific educational materials and it functioned as a reminder at the time of antibiotic assessment. Suggestions were offered in a noncoercive manner and were removed from the medical record within 24 hours. The authors believe that the success of the program was related to the focus on updating and expanding infectious disease knowledge, local resistance patterns, cost issues and antimicrobial options.
The authors conclude that 50 percent of patients in this study who were initially treated with parenteral antibiotics could have their regimens refined after three days of antibiotic therapy and that these modifications could be made safely and economically. The authors believe that their approach successfully guided physicians to the use of appropriate and cost-effective antibiotic alternatives without sacrificing the quality of care provided. By not interfering with the physician's choice of initial antibiotic therapy, diversity of utilization is maintained and the likelihood of developing antimicrobial resistance is lessened. This intervention also served as an acceptable quality assurance measure for the Joint Commission on Accreditation of Healthcare Organizations.
BARBARA APGAR, M.D., M.S.
Fraser GL, et al. Antibiotic optimization. An evaluation of patient safety and economic outcomes. Arch Intern Med 1997;157:1689-94.
Oral Contraceptives, HRT and Risk of Thromboembolism
Results of observational studies performed in the 1960s and 1970s led to the conclusion that use of oral contraceptive agents and hormone replacement therapy should be avoided in women with a history of venous thromboembolism because of an increased risk of recurrent thromboembolism. Estrogen is the purported thrombogenic factor. Douketis and associates analyzed the literature to determine whether such a risk is valid and whether the current practice of not prescribing oral contraceptives or hormone replacement therapy in women with previous venous thromboembolism is justified.
A MEDLINE search was performed and each study was rated according to methodologic quality. The rating scale for methodologic quality was as follows: level 1--four out of four essential methodologic criteria were present and the potential for bias and inaccuracy was low; level 2--three of four essential methodologic criteria were present and the potential for bias and inaccuracy was moderate; level 3--two or fewer essential methodologic criteria were present and the potential for bias and inaccuracy was high. Because of recent concern about the thrombogenic potential of third-generation oral contraceptives, the results of studies with these agents were evaluated separately. A total of 35 studies were included in the analysis.
The authors found that the methodologic quality of the studies investigating the risk of venous thromboembolism in oral contraceptive users and in women receiving hormone replacement therapy was highly variable. No study was rated as demonstrating level 1 evidence; 14 were rated as level 2, and 21 as level 3.
Some of the methodologic errors included diagnostic suspicion bias from previous knowledge of oral contraceptive use, failure to use accurate diagnostic tests to evaluate venous thromboembolism and biased interpretation of findings. The use of subjective and inaccurate diagnostic methods combined with previous knowledge of oral contraceptive use would probably lead to greater diagnostic misclassification in oral contraceptive users than in nonusers and an exaggeration of the risk of thromboembolism with oral contraceptive use.
With respect to the oral contraceptive studies, the pooled risk ratios were 3.0 in case-control studies, 4.8 in retrospective cohort studies, 2.4 in prospective studies and 1.1 in randomized controlled trials. The association between oral contraceptive use and thromboembolism was weaker in studies that used objective diagnostic data than in studies that used subjective data. Mortality studies found no significant association or reported deaths from pulmonary embolism.
The authors examined nine studies of hormone replacement therapy and found that the majority were of such poor methodologic quality that definitive conclusions were precluded. They note that the biologic plausibility of a strong association between hormone replacement therapy and thromboembolism is weak. The risk with hormone therapy would be expected to be lower than that with oral contraceptives because of the physiologic doses used in hormone replacement therapy. It also has not been determined that hormone therapy causes changes in coagulation parameters.
The authors conclude that an association between oral contraceptive use and venous thromboembolism is probably valid, but the magnitude of the risk is likely exaggerated. Results of the pooled analysis demonstrate that avoidance of oral contraceptive use in women with a history of venous thromboembolism is prudent. Women with known thrombophilic status should avoid both oral contraceptive agents and hormone replacement therapy, whether or not they have previously had venous thromboembolism. Because of the paucity of data on an association between hormone therapy and venous thromboembolism, the authors believe more studies are needed before definitive conclusions can be made.
BARBARA APGAR, M.D., M.S.
Douketis JD, et al. A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy. Arch Intern Med 1997;157:1522-30.
EDITOR'S NOTE: The recommendation that third-generation oral contraceptive agents be avoided was based on the findings of three epidemiologic case-control studies that linked the use of agents containing desogestrel or gestodene with an increased risk of nonfatal venous thromboembolism, as compared with the risk associated with oral contraceptives that contain levonorgestrel. The increase was 10 to 15 cases of venous thromboembolism per 100,000 in users of oral contraceptive agents that contain levonorgestrel and 20 to 30 cases per 100,000 in women taking oral contraceptives that contain gestodene or desogestrel. A fourth study, which was not part of the original investigation that led to the recommendation that third-generation agents be avoided, evaluated 12 oral contraceptive formulations and demonstrated no risk differences for venous thromboembolism among the various agents, including those containing gestodene and desogestrel. Epidemiologic studies have demonstrated that the risk of thromboembolism is related to the estrogen component, because the progestational agent has little effect on clotting parameters and is not thrombophilic. For this reason, the biologic plausibility of the results of the three case-control studies is weak.
B.A.
Macrosomia, Method of Delivery and Birth Injury
Increased birth weight is associated with more difficult delivery and increased rates of neonatal injury. A number of studies have used shoulder dystocia and initial injury rates as the outcome measures. The association between method of delivery and birth injury has been studied, but conclusions have varied. Kolderup and colleagues examined the association between the delivery method and persistent birth injury in infants with birth weights of 4,000 g (8 lb, 13 oz) or greater.
A total of 2,924 macrosomic infants were included in the study. The outcomes in these infants were compared with outcomes in 16,711 infants with birth weights from 3,000 g (6 lb, 10 oz) up to 4,000 g (8 lb, 13 oz).
A total of 48 injuries were diagnosed in the macrosomic cohort, for an overall injury rate of one injury per 61 deliveries (1.6 percent). Injuries ranged from simple clavicular fractures to multiple nerve palsies. One infant in the macrosomic group died following a 30-minute dystocia. In contrast, the injury rate in the nonmacrosomic infants was one injury per 288 deliveries (0.35 percent).
The injuries sustained in the macrosomic group tended to be more severe and were more likely to persist. A total of 22 brachial plexus injuries occurred, and all five that persisted for as long as six months after birth occurred in macrosomic infants. The data indicated that macrosomia was associated with an increased risk of persistent injury (relative risk: 6.7), and the risk was strongest for forceps-assisted and spontaneous vaginal deliveries. Cesarean section was associated with minimal risk of injury in both study groups.
Delivery by forceps (low or outlet) correlated with an approximately fourfold greater risk of persistent clinical findings at age six months, compared with vaginal delivery or cesarean section in the infants weighing more than 4,000 g (8 lb, 13 oz). Vacuum delivery resulted in the same rates of injury, but the injuries had resolved by the six-month follow-up visit.
Analysis of the subgroup of macrosomic infants born to mothers with diabetes revealed that the cesarean section rate in this group approached 70 percent. Severe birth injuries occurred in three of 78 infants delivered vaginally.
The authors used their findings to calculate the number of additional cesarean sections that would have been required to prevent birth injury in all of the neonates in the macrosomic group. The data indicated that if all macrosomic infants could be identified antenatally, 258 additional cesarean sections would be needed to prevent one persistent injury.
The authors conclude that the outcomes in the infants in this study suggest that a trial of labor is recommended even for macrosomic infants. Although persistent injury is more common in macrosomic infants delivered by forceps, the rate of documented lasting sequelae is very low. This low rate of persistent injury, combined with the current limitations of estimating the weight of large fetuses, supports the careful and judicious use of operative vaginal delivery for infants with suspected macrosomia.
BARBARA APGAR, M.D., M.S.
Kolderup LB, et al. Incidence of persistent birth injury in macrosomic infants: association with mode of delivery. Am J Obstet Gynecol 1997;177:37-41.
Laparoscopy vs. Laparotomy for Benign Ovarian Masses
Laparoscopy is being used with increasing frequency in the surgical management of benign ovarian masses. Despite the widespread use of laparoscopy for excision of ovarian masses and reported reductions in operative morbidity, hospital stay and recovery time, only a few studies have compared this technique with conventional laparotomy. Yuen and associates compared outcomes in patients who were randomly assigned to laparoscopy or laparotomy for the management of benign ovarian masses.
A total of 102 patients with tumors identified as benign by ultrasonography were included in the study. The mean surgery time did not differ between the two groups. Blood loss was significantly lower in the laparoscopy group, but no difference was apparent between the two groups in the postoperative change in hemoglobin level. The mean diameter of the tumors was 5.6 cm in the laparoscopy group and 5.7 cm in the laparotomy group.
All laparoscopic procedures were successfully completed. Surgical morbidity was significantly lower in the laparoscopy group than in the laparotomy group. This difference was mainly the result of the lower incidence of postoperative fever and urinary retention in the patients undergoing laparoscopy. The level of postoperative pain was significantly higher in the laparotomy group in the immediate postoperative period and within the first 24 hours after surgery. Analgesia was not required postoperatively in 54 percent of the patients in the laparoscopy group, compared with 10 percent of the laparotomy group.
The mean hospital stay was significantly shorter in the laparoscopy group (2.6 days versus 4.9 days), and patients who underwent laparoscopy were able to return to work sooner (17.9 days versus 30.4 days). They resumed oral intake sooner and were able to ambulate earlier in the course of recovery. More patients in the laparoscopy group were able to resume sexual activity within the first two weeks after operation. Patients in the laparoscopy group were more satisfied with the appearance of their surgical scar.
The authors note that the reported benefits of laparoscopic surgery generally are reported in studies conducted by very experienced surgeons. Although the laparoscopic approach is less invasive than laparotomy, the decision to perform one procedure or the other should be based on the same clinical criteria. The laparoscopic approach to the surgical management of benign ovarian masses offers a reduced hospital stay and recovery time. In the authors' opinion, it should replace laparotomy in the management of benign ovarian masses.
BARBARA APGAR, M.D., M.S.
Yuen PM, et al. A randomized prospective study of laparoscopy and laparotomy in the management of benign ovarian masses. Am J Obstet Gynecol 1997;177: 109-114.
Influenza Vaccine 1997-1998: An Overview and Comparison
A new intramuscular trivalent influenza vaccine is available for the current influenza season. Except for one new antigen (H1N1 antigen), the antigen mix in the current vaccine is the same as last year's. Although it was anticipated that a new nasal spray flu vaccine would be available this year, it has not yet received approval from the U.S. Food and Drug Administration. Consultants from the Medical Letter on Drugs and Therapeutics review current data for the new influenza vaccine.
Comparison of Influenza Vaccines Vaccine Preparation Available forms* Cost †
Fluzone Whole virus ‡
Split virusVial
Vial
10 syringes$32.50
32.50
42.50FluShield Split virus Vial
10 syringes38.50
50.00Fluvirin Purified
surfaceVial
10 syringes34.50
47.00
*--Each vial contains 5 mL (10 doses); syringes are sold in boxes of 10, each containing one 0.5-mL dose.
†--Estimated cost to the pharmacist based on average wholesale prices, rounded to the nearest half dollar, in Red book. Montvale, N.J.: Medical Economics Data, 1997. Cost to the patient will be higher, depending on prescription filling fee.
‡--Not recommended for use in children.
Adapted with permission from Influenza vaccine, 1997-1998. Med Lett Drugs Ther 1997;39(1009):85-6.
Influenza vaccination is recommended for elderly and other high-risk patients, their household contacts and health care personnel who may be in contact with them. The vaccination of healthy working adults and children may prevent household spread of the disease. Pregnant women can be vaccinated safely. There is an increased risk of influenza complications in women in the second and third trimesters of pregnancy.
Outbreaks of influenza usually reach a peak between late December and early March and may continue into the spring in some areas. Following vaccination, protection from influenza generally begins one to two weeks after injection and may last six months or longer. Elderly persons may not maintain serum antibody levels for six months and may fall below protection levels in four months or less. The optimal time for influenza vaccination is from October through mid-November, but vaccination any time from September to the end of the influenza season is appropriate.
Dosage recommendations differ for adults and children. A single intramuscular 0.5-mL dose of the vaccine is recommended for adults and for children who are at least three years of age. Children from six to 35 months of age should receive a dose of 0.25 mL. Children younger than nine years of age receiving the vaccine for the first time should receive two doses at least four weeks apart.
Because the influenza vaccine is made from inactivated virus grown in eggs, hypersensitivity reactions can occur, although they are rare. Occasionally, soreness may persist for one to two days at the injection site. Fever, myalgia and malaise can last one or two days but usually occur in young patients with no previous exposure to influenza antigens. Some reactions in children can be averted by administering split-virus and purified-surface-antigen formulations (see the accompanying table).
Consultants from the Medical Letter recommend influenza vaccination for high-risk persons and the elderly, their household contacts and health care workers. Adverse reactions are rare and can usually be averted by altering the dosage recommendations.
BARBARA APGAR, M.D., M.S.
Medical Letter Consultants. Influenza vaccine, 1997-1998. Med Lett Drugs Ther 1997:39(1009):85-6. *
"Tips from Other Journals" are written by the medical editors of American Family Physician.
Copyright © 1998 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.
