Tips from Other Journals
Should Patients With GERD Be Treated Continuously?
Continuous treatment with proton pump inhibitors has been widely recommended for long-term management of symptomatic gastroesophageal reflux disease (GERD). However, many patients, particularly those believed to have mild or moderate disease, are given only a short course of medication during symptomatic periods. Bardhan and colleagues studied the effectiveness of intermittent short courses of proton pump inhibitor therapy to control GERD symptoms over a 12-month period.
Patients were recruited for the study from 56 general medical practices in several European countries. Inclusion criteria included normal or mild erosive changes on endoscopy and a history of moderate to severe heartburn that interfered with normal activities for more than two days a week within a two-week period. Patients were randomized to receive omeprazole in a dosage of 10 mg daily, omeprazole in a dosage of 20 mg daily or ranitidine in a dosage of 150 mg twice daily for an initial two-week period. Those who were asymptomatic after seven days were then followed for 12 months to monitor recurrence. Patients who continued to have symptoms received either a double dosage of medication or their initial dosage for another two weeks. Those who were asymptomatic after the second treatment period also entered the follow-up study.
During the follow-up period, patients received no additional treatment unless they reported moderate to severe heartburn at least two days a week within a two-week period or if they took more than three antacid tablets daily to control symptoms. For each recurrence, patients received two or four weeks of the dosage of medication that had resolved their symptoms. Patients were reassessed every three months.
A total of 704 patients enrolled in the study. Of these, 526 reached a treatment-related end point. The median number of days without medication in this group of patients was 281. Recurrence was infrequent, with 40 percent of patients having no relapse, 30 percent having only one, 15 percent having two and 8 percent having three relapses. Symptom control at two weeks was a powerful predictor of no relapse. The only factor linked to relapse was smoking. Omeprazole was superior to ranitidine in controlling symptoms after two weeks, particularly in the higher dosage. However, by the end of 12 months, approximately 22 to 27 percent of patients in each treatment group required long-term maintenance therapy. Of note, intermittent therapy with an initial dosage of 20 mg of omeprazole was deemed the most cost-effective over a 12-month period.
The authors conclude that intermittent treatment is a simple yet practical strategy in general practice, where most of these patients are seen. Intermittent treatment controls the symptoms of moderate, uncomplicated GERD in more than one half of all patients. Relapses are relatively infrequent and usually can be controlled with a short course of treatment.
ANNE D. WALLING, M.D.
Bardhan KD, et al. Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. BMJ February 20, 1999;318:502-7.
Thrombosis, Stress Ulcers and Catheter-Related Infection
The major complications that occur in critically ill patients are (1) deep venous thromboembolism (DVT), (2) stress-related upper gastrointestinal bleeding and (3) infections related to vascular catheters. Saint and Matthay reviewed the literature to identify and recommend strategies that have been shown to reduce the risk of these complications in critically ill patients.
The authors reviewed the literature on the effectiveness of unfractionated heparin, low-molecular-weight heparin and intermittent pneumatic compression in preventing DVT. In a study of patients with heart failure or respiratory infection, the incidence of DVT was 4 percent in patients who received 5,000 U of low-dose unfractionated heparin every eight hours, compared with an incidence of 26 percent in patients who did not receive heparin. In a study of 1,358 medical patients, the mortality rate in patients receiving low-dose unfractionated heparin was 7.8 percent, compared with a mortality rate of 10.9 percent in patients who did not receive prophylaxis. In a randomized study of 166 medical patients, no significant difference in the incidence of DVT was observed between the patients who received low-molecular-weight heparin and the patients who received low-dose unfractionated heparin.
The authors' recommendations for prevention of DVT in critically ill patients are as follows: (1) Most critically ill patients who are at moderate or high risk of venous thromboembolism should receive prophylaxis with heparin. (2) Either low-dose unfractionated heparin or low-molecular-weight heparin is acceptable in critically ill patients. Low-molecular-weight heparin may be preferred in patients whose outcome may be compromised by minor bleeding or heparin-induced thrombocytopenia. (3) In patients with contraindications to heparinization, intermittent pneumatic compression may be appropriate, although no studies of its use in critically ill medical patients have been performed.
Studies have shown that mechanical ventilation and coagulopathy are associated with an increased risk of stress-related upper gastrointestinal bleeding. Mechanical ventilation and coagulopathy were the only risk factors identified in a study of 179 critically ill patients, of whom 14 percent had evidence of occult or overt bleeding. This association was also found in a study of 2,252 critically ill patients and surgical patients.
The authors evaluated the results of studies that compared histamine H2-receptor antagonists, sucralfate and antacids in preventing stress-related gastrointestinal bleeding. H2-receptor antagonists and antacids have been implicated as possible risk factors for nosocomial pneumonia in critically ill patients. A meta-analysis published in 1996 pointed to a significantly reduced incidence of clinically important bleeding in patients who received H2-receptor antagonist prophylaxis. However, a trend toward an increased risk of pneumonia and death was noted in these patients. A study that compared use of ranitidine and sucralfate in 1,200 patients requiring mechanical ventilation revealed that the incidence of clinically important bleeding was significantly lower in the ranitidine group (1.7 percent versus 3.8 percent in the sucralfate group). Ventilator-associated pneumonia was nonsignificantly decreased in the ranitidine group (16.2 percent versus 19.1 percent).
The authors' recommendations for prevention of stress-related gastrointestinal bleeding are as follows: (1) An H2-receptor antagonist prevents upper gastrointestinal bleeding in critically ill patients, but clinical studies have not demonstrated a mortality benefit. (2) Prophylaxis may be warranted in high-risk patients, such as those with respiratory failure or coagulopathy. (3) If prophylaxis is used, the choice between an H2-receptor antagonist and sucralfate may depend on the expected duration of mechanical ventilation (see accompanying algorithm).
Prophylaxis of Stress-Related Upper Gastrointestinal Bleeding Algorithm for prophylaxis of stress-related upper gastrointestinal bleeding. *--Decision mode is based on insufficient and conflicting data.
Reprinted with permission from Saint S, Matthay MA. Risk reduction in the intensive care unit. Am J Med 1998;105:515-23.
The risk of vascular catheterrelated infection depends on the length of time the catheter remains in place and the location of the catheter. One study of pooled data from 25 trials revealed that the risk of infection with a peripheral venous catheter was 1.3 percent per day; with a systemic arterial catheter, it was 1.9 percent per day; and with a central venous catheter, the risk was 3.3 percent per day.
The authors compared the literature on four methods of preventing catheter-related infections: the use of silver-impregnated cuffs attached to central lines, the use of antibacterial- or antiseptic-impregnated catheters, routine catheter changes, and the use of chlorhexidine gluconate as a skin antiseptic. Given the increased cost of silver-impregnated cuffs--$30 more per catheter--the authors believe efficacy should be established before routine use can be recommended.
Four studies have shown that triple-lumen central catheters coated or impregnated with antibacterials or antiseptics reduce the rate of bacterial colonization. Two studies did not show such a benefit, but the authors note that these two studies were flawed.
Although changing the catheter is thought to reduce the risk of catheter-related infections, this strategy does not appear to be supported by clinical studies. Two studies showed that the rate of infection did not differ between the group having frequent (i.e., weekly or every three days) catheter changes and the group having less frequent changes.
Clinical studies suggest that the best antiseptic agent for cleansing the skin in preparation for catheter insertion is chlorhexidine gluconate. In a randomized trial of patients with central venous catheters or arterial catheters, patients in whom chlorhexidine gluconate was used had a local infection rate of 2.3 percent, compared with infection rates of 7.1 percent for alcohol and 9.3 percent for povidone-iodine.
The authors' recommendations for prevention of vascular catheterrelated infections are as follows: (1) Compared with gauze dressing, transparent dressings may increase the risk of local infection, but the benefits may justify the use of transparent dressings. (2) Chlorhexidine gluconate should be used for disinfecting the skin before insertion of a catheter. (3) A central venous triple-lumen catheter impregnated with an antibacterial agent should be considered for patients who need short-term (less than seven days) central line access and who remain at high risk of infection. (4) Central venous, pulmonary arterial and systemic arterial catheters should be changed only when there is a clear indication to do so. (5) Pulmonary arterial catheters should be used cautiously.
GRACE BROOKE HUFFMAN, M.D.
Saint S, Matthay MA. Risk reduction in the intensive care unit. Am J Med December 1998;105:515-23.
Inhaled Steroids Not Linked to Congenital Malformations
Asthma is relatively common in pregnant women, but use of asthma medications in early pregnancy raises concerns about birth defects. Systemic glucocorticoids, such as budesonide and other inhaled steroids, have been linked to cleft lip and cleft palate in animal studies. In the United States, these steroids are classified as category C agents, indicating a teratogenic risk in animals and insufficient data in humans. Kallen and colleagues evaluated data on births in Sweden to identify an association between inhaled budesonide and congenital malformations.
Medical records of women who used inhaled budesonide during early pregnancy were identified from the Swedish Medical Birth Registry database. Information on possible congenital malformations in infants was obtained from coding information recorded at birth and from the Registry of Congenital Malformations. Data from these two sources were thought to identify 80 to 90 percent of all infants with severe malformations.
A total of 2,014 infants of women who had used budesonide in early pregnancy were identified. Most of the women (1,675) had also used other asthma medications. Seventy-five infants in the study group (3.8 percent) had severe congenital malformations, compared with 3.5 percent of infants in the general population. About one half of these infants had major structural defects, such as facial clefts and cardiac defects, and the rest had what are considered mild anomalies. Overall, the incidence of birth defects in the study group was similar to that of the general population.
The authors conclude that use of inhaled budesonide in early pregnancy is unlikely to be associated with a significant teratogenic risk.
ANNE D. WALLING, M.D.
Kallen B, et al. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol March 1999;93:392-5.
Do Doulas Have a Positive Effect on Outcome of Labor?
Experienced lay women, or doulas, who provide continuous emotional support to women in labor have been credited with improving many aspects of childbirth. The latter include reducing the number of operative deliveries and the use of analgesia and anesthesia, the length of labor and negative psychosocial outcomes. Most studies of the effect of doulas in the United States have focused on the support of young, nulliparous mothers from low-income groups. Little is known about their effect on other populations of women in the United States, particularly middle-class, married women whose spouses or other companions stay with them throughout labor and delivery. Gordon and colleagues studied the effectiveness of doulas in hospital-based births for women enrolled in a large Northern California health maintenance organization.
To be eligible for the study, women had to be nulliparous and in spontaneous labor after an uncomplicated pregnancy. Patients who met the criteria after initial assessment were randomized to receive usual care or doula-assisted delivery. All doulas had completed a community training program and had served as a doula at two or more deliveries. After every delivery, each doula was evaluated by the attending physician, a nurse and the patient. Patients in the doula group were interviewed by telephone four to six weeks after delivery.
A total of 314 women were enrolled in the study. Of these, 149 were in the doula group, and 165 received usual care. More than one half of the patients were white college graduates. Mean patient age was 29 years, and more than 80 percent of patients had attended childbirth preparation classes. Demographic information, stage of labor and types of support persons at the hospital were similar between groups. Rates of uncomplicated vaginal delivery, cesarean delivery, operative delivery and use of oxytocin or analgesics were also similar between groups. However, patients in the doula group were less likely to have epidural anesthesia (54 percent compared with 66 percent), even though slightly more women in this group had planned to request it compared with those in the usual care group. Women in the doula group were also more likely to rate the birth experience as good and to have positive perceptions about themselves and their bodies. No differences were documented in patients' descriptions of their labor or in postpartum measures of self-esteem, including depression. More than 95 percent of women in each group breast-fed initially and both groups had very high rates of breast feeding after four weeks.
The authors conclude that doulas contributed positively to labor outcomes, even in this highly supported population, but the measurable benefits may be limited to a reduction in the use of epidural anesthesia and positive outcomes related to maternal perceptions of well-being. In all other areas, there were no substantial differences. Women who had doulas were very enthusiastic about their experience with them, and those who did not reported high interest in using doulas in future deliveries. The knowledge, support and reassurance that doulas provide during labor and delivery might restore the human aspect to childbirth.
ANNE D. WALLING, M.D.
Gordon NP, et al. Effects of providing hospital-based doulas in health maintenance organization hospitals. Obstet Gynecol March 1999;93:422-6.
Treatment of Patients with Epilepsy Emergencies
Patients with a seizure disorder are commonly seen in the primary care setting. Some of these patients present with status epilepticus. The cardinal feature of status epilepticus is continuous or repeating seizures that occur so rapidly that the patient does not recover consciousness between them. Status epilepticus is a danger to the patient and a treatment challenge to the physician. Willmore reviews the treatment of epilepsy emergencies, with special emphasis on the management of patients with status epilepticus.
The author presents a timetable for the appropriate treatment of status epilepticus (see accompanying table). After the diagnosis has been confirmed, treatment is initiated with either acute emergency management or rational drug administration. Emergency care is designed to prevent injury, whereas drug treatment is guided by its ability to limit morbidity associated with systemic changes or seizure-induced neuronal damage.
Timetable for the Treatment of Status Epilepticus
Minutes
Action
0 to 5 Confirm diagnosis by observing seizure activity or one additional seizure Administer oxygen by nasal cannula or mask; control head position and airway; evaluate need for intubation if ventilatory assistance is needed Obtain and record vital signs; continue to observe; treat any abnormalities; establish ECG recording Obtain IV access, keep open with 0.9 percent saline; use glucometer or draw venous blood for glucose, serum chemistries, hematology, toxicology and AED levels Evaluate oxygenation with oximetry or arterial blood gas determinations 6 to 9 If patient is hypoglycemic or if blood sugar measurement is not available, give glucose: adults, 100 mg IV thiamine followed by 50 mL of 50 percent glucose by IV push; children, 2 mL per kg of 25 percent glucose 10 to 20 In adults, administer IV either 0.1 mg per kg of lorazepam at 2 mg per minute up to 4 mg total dose or 0.2 mg per kg of diazepam at 5 mg per minute up to 20 mg maximum Diazepam can be repeated if seizures continue after 5 minutes Diazepam must be followed by loading with phenytoin 20+ Load with 20 mg per kg phenytoin no faster than 50 mg per minute in adults and 1 mg per kg per minute in children; monitor ECG and blood pressure during infusion; IV fluids must be 0.9 percent saline Fosphenytoin may be given at 150 phenytoin-equivalents per minute as a safe substitute for
phenytoin>60 If status continues after 20 mg per kg of phenytoin, give additional phenytoin or fosphenytoin at 5 mg per kg until a maximum of 30 mg per kg If status persists, give 20 mg per kg of IV phenobarbital at 60 mg per minute Expect apnea, particularly if the patient has received benzodiazepines Assist ventilation; intubation will be required If status persists, use anesthesia with pentobarbital, midazolam or propofol; intubation, ventilation and vasopressors will be required
(ECG=electrocardiogram; IV=intravenous; AED=anti-epileptic drug)
Reprinted with permission from Willmore LJ. Epilepsy emergencies. The first seizure and status epilepticus. Neurology 1998;51(suppl 4):S34-8.
The author concludes that the cause of status epilepticus must be determined in any patient who presents with this disorder. Investigations should include brain imaging studies to rule out any mass lesions or evidence of ventricular obstruction. If the patient is febrile and there is no evidence of mass lesions or ventricular obstruction, a lumbar puncture should be performed.
JIM NUOVO, M.D.
Willmore LJ. Epilepsy emergencies. The first seizure and status epilepticus. Neurology November 1998;51(suppl 4):S34-8.
Esophageal Reflux a Trigger for Asthma Symptoms
Several studies have noted an association between gastroesophageal reflux disease (GERD) and asthma symptoms. Moreover, treatment of reflux may improve or diminish asthma symptoms in patients who have both conditions. Harding and colleagues examined the prevalence and severity of GERD in patients with asthma.
Study subjects had undergone esophageal pH testing over a five-year time period. All subjects with a self-reported diagnosis of asthma were selected from this group. The diagnosis of asthma was confirmed using criteria of the American Thoracic Society (ATS). The criteria included a 20 percent improvement in forced expiratory volume in one second (FEV1) with use of bronchodilators or a decrease in FEV1 of 20 percent or greater on methacholine challenge.
GERD was considered present in patients if one or more acid exposure times were abnormal on either the proximal or the distal esophageal pH probe. Specific values were used to quantify the total percentage of the time that the pH measurement was less than 4 during a 24-hour period, compared with healthy volunteers. In addition, ambulatory pH monitoring allowed the patients to record respiratory symptoms (wheezing, cough, shortness of breath) and later correlate these symptoms with esophageal acid events. A positive correlation was made if, when the pH was less than 4, the patient had respiratory symptoms that coincided with the acid episode or occurred less than five minutes later.
From an intial group of 1,983 patients who underwent esophageal pH testing, 358 reported a history of asthma. Of this group, 199 met the inclusion criteria after the ATS guidelines were used to confirm a diagnosis of asthma. The patients were predominantly white women with a mean age of about 45 years. Of the 199 study subjects, 82 percent had a history of reflux symptoms and, after esophageal pH testing was completed, 72 percent had abnormal results. Among the asthmatic patients who did not have reflux symptoms, 29 percent were found to have acid reflux as determined by pH testing. Respiratory symptoms strongly correlated with symptoms of GERD. In symptomatic patients, 64 percent of episodes of wheezing or shortness of breath were associated with esophageal acid, as were 98 percent of episodes of cough.
Among all patients with asthma and GERD defined by pH testing, 78.8 percent of respiratory symptoms were associated with esophageal acid. It was also determined that in patients with symptomatic GERD, reported episodes of heartburn, nausea and regurgitation correlated strongly with the presence of esophageal acid. Interestingly, no difference was noted in lower esophageal sphincter pressure in the 62 symptomatic patients compared with the 56 asymptomatic patients receiving theophylline for asthma.
The authors conclude that there is a strong correlation between GERD and the symptoms of asthma. In patients with asthma and symptomatic GERD, an empiric trial of antireflux medication should be used, and pH testing is probably not necessary. Twenty-four-hour pH monitoring should be considered in patients with asthma that has been difficult to control, since up to one third of these patients may have asymptomatic acid reflux.
JEFFREY T. KIRCHNER, D.O.
Harding SM, et al. 24-h esophageal pH testing in asthmatics. Respiratory symptom correlation with esophageal acid events. Chest March 1999;115:654-9.
Can HPV Infection Be Sexually Transmitted Between Women?
Over 2 million women in the United States describe themselves as lesbians, and even more women report that they have sex with other women. Despite the fact that cervical neoplasia develops in women who report that they have never had sex with men, little is known about the prevalence of human papillomavirus (HPV) infections in this population. The frequency with which lesbians and bisexual women acquire sexually transmitted diseases is assumed to be similar to that of heterosexual women. However, these women tend to have Papanicolaou smears less frequently than their heterosexual counterparts. Marrazzo and associates evaluated the prevalence of HPV infection in this population and the frequency with which they report having Pap smears.
Women recruited for the study reported having sex with other women within the past year. On entry to the study, a detailed medical and sexual history was obtained, and a pelvic examination and colposcopy of the cervix were performed. Specimens were collected so that a Pap smear and HPV DNA testing by polymerase chain reaction (PCR) could be completed. All Pap smears were read by the same cytopathologist, and the HPV DNA testing was done in one laboratory.
A total of 149 women qualified for the study. Most reported having had sex with a man sometime in the past, but only 24 percent reported doing so within the previous year. More than one half of the women had had sex with only one female partner within the past year. HPV infection was detected by PCR in 45 women, but none of these gave a history of genital warts and only two had had sex with a man who had genital warts. Cigarette smoking, history of abnormal Pap smear and age between 25 and 30 years were also associated with a higher risk for HPV DNA. Thirteen women in this group had abnormal results on their Pap smears. Of these, three reported that they had not had sex with a man, and three reported having sexual contact with a woman who had genital warts. Squamous intraepithelial lesions (SIL) were found in six women, and atypical squamous cells of undetermined significance (ASCUS) were found in seven others. HPV DNA was found in five of the six women with SIL. The mean interval for Pap smears in this group was 21 months, compared with eight months in heterosexual women who were matched for age and attended the same clinic.
The authors conclude that HPV infection can be sexually transmitted between women. In this study, 30 percent of the women had HPV infections, along with a significant number of abnormal results on Pap smears. Despite these results, women who have sex with women wait longer between Pap smears than do their heterosexual counterparts. The authors concede that because the size of their study group was small, more research is needed. Until more definitive data are obtained, the recommended interval between Pap smears should be the same for all women, regardless of sexual orientation.
KARL MILLER, M.D.
Marrazzo JM, et al. Genital human papillomavirus infection in women who have sex with women. J Infect Dis December 1998;178:1604-9.
Diagnosing Severe Dizziness in Older Adults
Dizziness is a common symptom in older adults; it is also associated with a greater risk of disability. Appropriate treatment or referral depends on accurate diagnosis, which is usually undertaken at the primary care level. Lawson and associates conducted a prospective case control study of the clinical features of dizziness in elderly patients to determine if diagnosis of this condition can be improved.
Fifty patients older than 60 years of age who presented with dizziness were matched with 22 control subjects who did not have dizziness. All patients were interviewed and examined by a single clinician. A description of the symptoms associated with the dizziness, provoking factors and medical history were sought during the interview. The clinical examination included mental status testing, a full neurologic examination and psychiatric screening, as well as routine laboratory tests. Patients were then referred to a neurocardiovascular investigation unit and an otolaryngology department. At that point, all patients had electrocardiography, ambulatory blood pressure monitoring and orthostatic blood pressure measurements. Tilt testing, otoscopy, Weber and Rinne testing, and audiometry were also done. If indicated, patients had echocardiograms, carotid Doppler studies and computed tomography of the head.
After completion of the work-up, an attributable diagnosis was made. The initial history and physical examination were used to determine which factors predicted the eventual diagnosis. Dizziness was classified, when possible, into one of the following diagnoses: (1) peripheral vestibular disorder (including benign paroxysmal positional vertigo, vestibular neuronitis, labyrinthitis and Meniere's disease); (2) orthostatic hypotension; (3) arrhythmia; (4) carotid sinus hypersensitivity; (5) vasovagal syncope; or (6) central neurologic disorders. In the patients with dizziness, symptoms had been present for two weeks to 30 years and occurred an average of three times per week. Symptoms lasted three minutes on average, but in some patients as long as 180 minutes. About 26 percent of patients also had syncope, 16 percent had unexplained falls and 4 percent experienced both syncope and falls.
A cardiovascular disorder was the attributable diagnosis for the dizziness in 28 percent of patients, while 18 percent were diagnosed with a peripheral vestibular problem and 14 percent had a central neurologic cause. Multiple diagnoses were present in 18 percent of patients, and no diagnosis was made in 22 percent. A variety of associated symptoms or descriptions made a cardiovascular diagnosis more likely: syncope, a "lightheaded" dizziness, pallor with the dizziness or a history of other cardiovascular problems (such as angina or peripheral vascular disease). Dizziness during prolonged standing was also associated with a cardiovascular diagnosis. When the patient described the dizziness as vertigo, the diagnosis was more likely to be peripheral vestibular dysfunction. Some physical examination maneuvers, namely visual acuity testing, the Weber and Rinne tests and the Hallpike maneuver, did not help to predict the attributable diagnosis. Similarly, routine laboratory testing, which included urinalysis, did not lead to a diagnosis.
The authors conclude that a thorough history, a focused examination and appropriate referral (if needed) may allow appropriate risk factor modification and treatment in elderly patients with dizziness. Cardiovascular assessment is much more likely to lead to an accurate diagnosis of dizziness than is otolaryngologic evaluation.
GRACE BROOKE HUFFMAN, M.D.
Lawson J, et al. Diagnosis of geriatric patients with severe dizziness. J Am Geriatr Soc January 1999;47:12-7.
Sonography in Evaluation of Lower Abdominal Pain
Abdominal pain is a common complaint in children and young adults, resulting in a significant number of visits to the hospital emergency department. Of all possible diagnoses associated with abdominal pain, acute appendicitis is the most serious and perhaps one of the most difficult to diagnose based solely on clinical findings. For more than 10 years, sonography has been considered an accurate diagnostic tool for examining patients with acute appendicitis. However, the role of sonography in the initial diagnosis of lower abdominal or pelvic pain has not been well researched. Carrico and colleagues evaluated the impact of sonography on physicians' initial diagnostic confidence and their treatment of nontraumatic abdominal pain in children and young adults.
Children and young adults who presented to a large urban pediatric emergency department during a six-month period in 1997 with acute abdominal pain, pelvic pain, or both, and who underwent sonographic examination were eligible for the study. Physicians were asked to state the most likely diagnosis and then estimate the probability of that diagnosis both before and after the results of sonography were available. They were also asked to describe their treatment plan if sonography had not been performed.
Of the 101 patients who met the study criteria, data were collected for 94. Sonographic data significantly affected the initial diagnosis in 38 patients who were thought to have appendicitis after clinical examination. Of these patients, 20 (53 percent) had a change in diagnosis after sonographic examination. The remainder of the total study group had abdominal conditions other than appendicitis. The use of sonography improved physicians' clinical confidence, particularly in those patients whose diagnoses changed after the procedure. In this group, there were no false-positive results, and the true negative rate was 100 percent. The treatment plans of 43 patients overall changed as a result of sonographic information. Before the sonography, physicians planned to discharge two and admit for observation 12 of the 17 patients with surgically proven appendicitis.
The authors conclude that sonography is an important tool in the assessment of abdominal or pelvic pain in children and young adults. Sonographic information changed initial diagnoses, increased clinical confidence and led to changes in treatment plans. In this study, the results of sonography reassured physicians that, in most instances, patients' abdominal pain did not require surgical intervention. For patients who had acute appendicitis, sonography reduced delays in diagnosis.
KARL MILLER, M.D.
Carrico CW, et al. Impact of sonography on the diagnosis and treatment of acute lower abdominal pain in children and young adults. Am J Roentgenol February 1999; 172: 513-6.
Treatment of Hypersexuality in Nursing Home Residents
Patients with dementia may become sexually disinhibited as cognitive deficits progress. This behavior may also be the result of other neurologic disorders or a side effect of medications used to treat Parkinson's disease. Both hypersexuality and paraphilias (such as voyeurism, exhibitionism, fetishism and pedophilia) can cause behaviors in elderly patients that are difficult to manage in the nursing home setting. Levitsky and Owens review case reports of pharmacologic agents that may be used to treat hypersexuality in the event that nonpharmacologic treatments are unsuccessful.
Several medications have been studied in the pharmacolgic treatment of sexually disinhibited behavior in elderly patients with dementia. These medications include antiandrogens, estrogens, gonadotropin-releasing hormone (GnRH) analogs and serotonergic agents. Antiandrogens are thought to reduce testosterone levels, which then impairs sexual functioning and eliminates hypersexual behavior. Medroxyprogesterone acetate and cyproterone acetate are the most commonly used antiandrogenic agents. Both of these medications can cause fatigue, weight gain and depression. In one study, patients were given medroxyprogesterone acetate in a dosage of 300 mg per week intramuscularly for one year. Undesirable behaviors were eliminated within two weeks of initiation of treatment, and at one-year follow-up, the effect continued in 75 percent of patients who received the treatment. Another study used medroxyprogesterone acetate in a dosage of 100 mg intramuscularly every other week and increased the dosage to 150 mg intramuscularly every other week, at which point all inappropriate behaviors were suppressed.
Estrogen has not been used often in the treatment of hypersexual behaviors. One study reported a significant reduction in these behaviors in 38 of 39 men who received estrogen either orally (0.625 mg daily) or in transdermal patches (0.05 to 0.10 mg). In another study, a 94-year-old man with dementia was treated with diethylstilbestrol (starting with a dosage of 1 mg per day); within the first week, his inappropriate sexual behaviors were successfully controlled.
GnRH analogs stimulate the secretion of follicle-stimulating hormone and luteinizing hormone, thereby increasing estrogen and androgen concentration and decreasing testosterone production. To maintain effectiveness, these medications must be used continuously and may cause hot flashes, decreased libido and erectile dysfunction. Leuprolide acetate has been reported to be successful in treating patients with hypersexual behavior or paraphilias.
Because hypersexual and paraphilic behaviors are thought by some to be related to obsessive-compulsive disorder, selective serotonin reuptake inhibitors (SSRIs) have been proposed as effective treatment agents. Others think that the antilibidinal effects of SSRIs explain their effectiveness. One patient was successfully treated with 20 mg per day of paroxetine. Other patients have had good results from treatment with clomipramine (a tricyclic antidepressant with some SSRI properties), titrated to a dosage of 150 to 175 mg per day. SSRIs have adverse effects that include nausea and vomiting, headache, fatigue and insomnia. Clomipramine is associated with both anticholinergic effects and orthostatic hypotension, and should therefore be used with caution in elderly patients.
The authors conclude that, while controlled trials have not been done, various pharmacologic methods (starting with SSRIs in most cases) have been reported to successfully control hypersexual behaviors and paraphilias in certain patients.
GRACE BROOKE HUFFMAN, M.D.
Levitsky AM, Owens NJ. Pharmacologic treatment of hypersexuality and paraphilias in nursing home residents. J Am Geriatr Soc February 1999;47:231-4.
Visual Criteria for Evaluating Pigmented Skin Lesions
Early detection and prompt excision of malignant melanomas offer the best chance of cure. A series of visual criteria were developed more than a decade ago to help physicians identify early melanoma and guide its treatment. The asymmetry, border, color and dimension (ABCD) criteria represent a practical but imperfect system for evaluation of skin lesions. As with any clinical diagnosis, the evaluation of a lesion using the ABCD criteria is highly subjective. Bono and associates tested the validity of the ABCD criteria compared with that of telespectrophotometric measurements in identifying malignant melanomas.
All patients enrolled in the study had cutaneous pigmented lesions that required surgical biopsy for early diagnosis of melanoma. Mean patient age was 40 years, and approximately twice as many women as men were enrolled. Lesions were located primarily on the trunk (63 percent), followed by the extremities (32 percent) and the head (5 percent). Before surgical excision, all lesions were evaluated with telespectrophotometry for roundness, smoothness, mean reflection (color) and size, the same features that comprise the ABCD criteria.
A total of 186 patients with 195 lesions were enrolled in the study. Of these, 77 were believed to be malignant melanomas and 118 to be benign skin lesions, based on clinical diagnosis alone. Pathology revealed that 53 of the lesions were melanomas, and the rest were benign skin lesions. Of interest, six of the melanomas were less than 6 mm in diameter. Telespectrophotometric measurements, particularly mean reflectance (color) and size, more reliably identified melanomas than the ABCD criteria. Of these, color was the most sensitive predictor. Roundness and smoothness did not contribute significantly to the diagnosis. Telespectrophotometric measurements also reliably distinguished dysplastic nevi from melanomas.
The authors conclude that the ABCD criteria are a simple, useful means of identifying malignant melanomas. However, to be more effective as a diagnostic tool, the criteria should be modified to account for changes in the characteristics of lesions. Of the information provided by telespectrophotometric measurements, the most important variable in distinguishing melanoma from nevi appears to be color. In this study, the darker the skin lesion, the more likely that it was a melanoma. Therefore, the authors recommend that the C in ABCD should represent "color darkness," as this distinction would increase the sensitivity of the ABCD criteria in identifying melanomas.
KARL MILLER, M.D.
Bono A, et al. The ABCD system of melanoma detection. A spectrophotometric analysis of the asymmetry, border, color, and dimension. Cancer January 1999;85:72-7.
Plain or Buffered Lidocaine for Neonatal Circumcision?
Parents are increasingly asking for safe and effective pain relief for their infants during circumcision. Use of a dorsal penile nerve block with lidocaine is believed to provide adequate pain relief, but many physicians do not use it, concerned that stinging from lidocaine at the injection site could add to the stress of the procedure. The time associated with administering the anesthetic may also be a factor. Buffered lidocaine has been shown to decease stinging and speed the anesthetic effect. Newton and colleagues compared the effectiveness of plain lidocaine with that of buffered lidocaine in reducing pain experienced during the injection and in providing pain relief during the procedure.
All healthy newborn boys circumcised at a large Midwestern hospital were eligible for the two-year study. Infants were randomized to receive 1 percent lidocaine, either as a simple solution or buffered with sodium bicarbonate. No other comfort measures were given. The circumcisions were performed using standard technique, and involved personnel knew which anesthetic was used on each infant. Heart rate and oxygen saturation were monitored continuously, and the infants were evaluated three times during the procedure using a behavioral scale based on levels of arousal.
A total of 194 infants were enrolled in the study, 92 in the plain lidocaine group and 102 in the buffered lidocaine group. No significant differences in heart rate, oxygen saturation, arousal score or general clinical observations were noted between groups. Minor bleeding occurred in a small percentage of infants in each group; otherwise, there were no complications.
The authors conclude that both solutions provided safe and effective anesthesia for the procedure. Both solutions appeared to have a similar onset of action and provided a comparable level of pain relief. The addition of a buffering agent to lidocaine did not influence anesthetic effectiveness, although other studies suggest that the rate of infiltration may be a significant factor. Less pain may be experienced when the anesthetic agent is infiltrated slowly.
ANNE D. WALLING, M.D.
Newton CW, et al. Plain and buffered lidocaine for neonatal circumcision. Obstet Gynecol March 1999;93:350-2.
A Patient-Centered Discussion of Advance Medical Planning
Although much has been written about the need for advance medical planning, only 33 percent of nursing home residents had living wills or health care proxies in one 1993 survey. Although establishing a patient's wishes for do-not-resuscitate (DNR) orders is important, a better approach to the discussion might be to have the patient rank three common goals of care as a basis for discussing his or her wishes. Gillick and colleagues conducted a prospective, descriptive study that examined three goals of care and five patterns of care to help patients plan for end-of-life care.
Five Major Patterns of Care for the Elderly Patient
The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication. The authors identified three principles of end-of-life care: (1) prolongation of life, (2) maintenance of function, both physical and cognitive, and (3) maximization of comfort. All clinically relevant rankings of these three goals were considered, leading to five major patterns of care--intensive, comprehensive, basic, palliative and comfort only (see accompanying table). In the intensive pattern of care, prolongation of life was ranked first, followed by maintenance of function and comfort. In the comprehensive pattern, the order was maintenance of function, prolonged life and comfort; in the basic care pattern, the order was maintenance of function, comfort and prolonged life; in the palliative pattern, the order was comfort, maintenance of function and prolonged life; and in the comfort-only pattern, the only goal was comfort.
The residents of a nursing home and their families attended a meeting to discuss these goals and patterns for end-of-life care. Within two weeks of the meeting, the residents or their surrogates were asked to determine their individual priorities for end-of-life care. Of the 38 patients who participated in the study, 21 participated directly and 17 were represented by their surrogates. Overall, 21 percent of study participants selected intensive care (33 percent of patients versus 6 percent of surrogates); 16 percent selected comprehensive care (28 percent of patients, zero percent of surrogates); 18 percent selected basic care (5 percent of patients, 35 percent of surrogates); 18 percent selected palliative care (5 percent of patients, 35 percent of surrogates); and 6 percent chose comfort care only (zero percent of patients, 12 percent of surrogates). Twenty-eight percent of patients and 12 percent of surrogates were unable to decide on a pattern of care or stated that they did not want think about these issues.
The authors conclude that while current DNR orders are important, they address only a small proportion of the medical decisions that must be made by or for a nursing home resident. The authors also acknowledge that this study did not determine whether the goals set were subsequently used to guide treatment decisions. As the nursing home population increases, further studies such as this one are clearly needed.
GRACE BROOKE HUFFMAN, M.D.
Gillick M, et al. A patient-centered approach to advance medical planning in the nursing home. J Am Geriatr Soc February 1999;47:227-30.
EDITOR'S NOTE: A variety of devices can facilitate the discussion of advance medical care. This study, which helps patients view various treatments (or lack thereof) as supporting one of three possible goals of care (prolonging life, maintaining function or maximizing comfort), is an elegant way to conceptualize a problem that is sometimes difficult for both the physician and the patient or surrogate. Of particular note is the large discrepancy between the patient's wishes and the surrogate's wishes. Although this result could be explained by a variety of study factors, it underscores the need to ask the surrogate what the patient would have wanted, not what the surrogate wants.
G.B.H.
Does Injectable Contraceptive Cause Bone Loss in Women?
Depot medroxyprogesterone acetate, an injectable contraceptive that is commonly used worldwide, has an impressive safety and efficacy record. However, recent studies have suggested that prolonged use may be associated with bone density loss, thus predisposing women who use this contraceptive to osteoporosis. Scholes and colleagues sought to verify the effect of depot medroxyprogesterone acetate on bone density in a population-based cross-sectional comparison of American women.
Women aged 18 to 39 years who were enrolled in a large group health plan participated in the study. A total of 183 women who were receiving depot medroxyprogesterone acetate injections were matched by age to control subjects attending the same clinic. Women who were pregnant, intending pregnancy or had any condition that could adversely influence bone density were excluded from the study.
At entry to the study, patients were measured and weighed, and completed extensive surveys that assessed demographic characteristics and factors affecting bone density. Bone densities were measured at proximal femur, lumbar spine and whole body.
The women using the injectable contraceptive were more likely than control subjects to be smokers, to be nonwhite, to be physically active and to be parous. They were also less likely to have completed high school, or report a previous fracture. Users reported first pregnancy at a younger age than control subjects.
The age-adjusted mean bone density levels for lumbar spine were significantly lower among users than among control subjects and lower at all other anatomical sites. After adjustment for other risk factors for reduced bone density, the differences were significant at the femoral neck, spine and trochanter. A significant dose-related response was found with the loss of bone density related to duration of medroxyprogesterone use. The most pronounced differences between users and control subjects were found in the youngest women (18 to 21 years).
The authors discuss the serious implications of their findings for the development of osteoporosis in users of this form of contraception. Inhibition of development of bone density in young women may lead to severe bone pathology at a younger age than in non-users. They are particularly concerned about the use of depot medroxyprogesterone in teenagers with other risk factors for low bone density.
ANNE D. WALLING, M.D.
Scholes D, et al. Bone mineral density in women using depot medroxyprogesterone acetate for contraception. Obstet Gynecol February 1999;93:233-8.
ERT and Breast Cancer Risk in Women with Prior Biopsies
The benefits of estrogen replacement therapy (ERT) in women have been well established. Some concern remains that estrogen may increase the risk of breast cancer, and it has been shown that unopposed estrogen use may lead to endometrial carcinoma. Whether ERT increases the risk of breast cancer in women who have had previous biopsies that revealed benign breast tissue has been unknown. On the contrary, before data were released in 1985, it was believed that these women had a two- to threefold elevation in breast cancer risk. Using data collected from the Nashville Breast Cohort, Dupont and colleagues assessed the risk of breast cancer in women who had histologically defined benign breast biopsies and had received ERT.
The women in the study included those who had undergone a breast biopsy that revealed benign breast parenchyma or fibroadenoma. Any woman who later was found to have breast cancer or carcinoma in situ treated by mastectomy was excluded from analysis. The use of ERT was defined as the use of noncontraceptive estrogens for at least one month at or after menopause or after 40 years of age. The age of menopause was considered to be the age at which a woman's menses had completely stopped, assuming this to be the case if a woman was given ERT after age 40. The actual age of menopause could not be determined in 20 percent of the women. Follow-up was terminated if the patients developed breast cancer (4.7 percent), underwent bilateral mastectomy for reasons other than breast cancer (3.8 percent), were lost to follow-up (2.9 percent), died from other causes (10.6 percent) or completed the study questionnaire (78.1 percent). The histologic slides of all patients, those with and without breast cancer, were reviewed by pathologists who had no knowledge of patient outcomes.
A total of 9,494 patients were in the original cohort and, after exclusion criteria were applied, 5,813 women were included in the analysis. More than 96 percent of the study subjects were white. The median follow-up was 20 years, which accounted for 190,845 woman-years of follow-up.
It was found that ERT users were younger at menopause (46 compared with 48 years of age), less likely to have had a natural menopause and more likely to have had children than the women who did not use ERT. There was a total of 444 confirmed cases of breast cancer in the entire cohort of women. However, there was no difference in the relative risk of invasive breast cancer in patients with proliferative breast disease identified on biopsy regardless of whether they received ERT. In women with an original diagnosis of complex fibroadenoma, the relative risk was 1.57 if they received ERT and 1.46 if they did not. In women who had neither a diagnosis of atypical hyperplasia nor fibroadenoma, these risks were 1.0 for the women in the ERT group and 1.27 for those who did not receive hormone therapy. The differences were not statistically significant. In addition, it was also found that a family history of breast cancer (a mother, sister or daughter) did not affect the risk in users versus nonusers of ERT.
The authors conclude that there is no increased risk of breast cancer associated with use of ERT in women who have undergone previous biopsies revealing benign breast tissue. Consequently, ERT is not contraindicated in this subgroup of patients once they become menopausal.
JEFFREY T. KIRCHNER, D.O.
Dupont WD, et al. Estrogen replacement therapy in women with a history of proliferative breast disease. Cancer March 15, 1999;85:1277-83.
Lovastatin in Adolescents with Familial Hypercholesterolemia
The age at which lipid-lowering drug therapy should be started in patients with familial hypercholesterolemia and premature coronary disease is not well defined, although there is agreement that drug therapy should be started in such patients if a low-fat diet fails to reduce the low-density lipoprotein (LDL) cholesterol level to below 160 mg per dL (4.2 mmol per L). Pharmacologic intervention is also generally advocated in patients without a family history of premature coronary disease if the LDL level remains above 190 mg per dL (4.9 mmol per L). Bile-acid sequestrants, which have a relatively long history of use in children with familial hypercholesterolemia, are generally the drugs of choice, but these agents do not have a major effect on LDL levels. Stein and colleagues conducted a study to determine if a statin (specifically, lovastatin) is safe and effective in the treatment of adolescent males with heterozygous familial hypercholesterolemia.
A total of 132 boys 10 to 17 years of age were enrolled in the double-blind, placebo-controlled study; 110 completed the 48-week study. In all of the boys, LDL levels (despite dietary measures) had measured at least 189 mg per dL (4.9 mmol per L). All of the subjects had a family history of one parent with similarly elevated LDL levels or of a parent who died as a result of coronary artery disease. Tanner stage was assessed at recruitment and at 24 and 48 weeks after study entry. Height, weight, lipid profile, liver function and diet were monitored periodically throughout the study. Dietary instruction was provided.
Lovastatin was started at a dosage of 10 mg per day and increased to 20 mg per day at the eighth week and to 40 mg per day at the 16th week. During the first 24 weeks, while the lovastatin dosage was being gradually increased, LDL and total cholesterol levels dropped in the lovastatin group but not in the placebo group. At 10 mg per day, the mean total cholesterol level declined by 13 percent and the mean LDL level declined by 17 percent. At 20 mg per day, the mean cholesterol and LDL levels dropped by 19 percent and 24 percent, respectively. When the lovastatin dosage was 40 mg per day (in the second 24-week period), the mean total cholesterol level was 20 percent lower than the baseline level, and the mean LDL level was 25 percent lower.
Changes in growth parameters did not differ between the lovastatin group and the placebo group. Alanine aminotransferase (ALT) levels gradually increased in both groups during the study period, but at 48 weeks, the differences were not significant. Aspartate aminotransferase (AST) and creatine kinase values remained unchanged.
The authors conclude that the use of lovastatin in boys with heterozygous familial hypercholesterolemia is both safe and effective. Although the LDL reductions were moderate, evidence suggests that even a modest decrease in adults can slow progression of coronary artery disease and reduce the risk of coronary events.
In a related editorial, Rifkind and associates laud Stein's group for conducting the study, stating that it begins to address concerns about prescribing statins for children with hereditary familial hypercholesterolemia. The editorial also points out some flaws in the study. For example, the safety evaluation failed to study the effects of lovastatin on cognitive and psychosocial function. Issues of compliance were not addressed. That said, the editorial emphasizes that hereditary familial hypercholesterolemia is easily diagnosed and should be treated as aggressively as possible in adolescent boys. The appropriate strategy for girls and young women, given their relatively later onset of clinical coronary heart disease, is less clear.
GRACE BROOKE HUFFMAN, M.D.
Stein EA et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia.: a randomized controlled trial. JAMA January 13, 1999;281:137-44, and Rifkind BM, et al. When should patients with heterozygous familial hypercholesterolemia be treated?[Editorial] JAMA January 13, 1999; 281:180-1.
The Role of Tobacco and Cocaine in Spontaneous Abortion
The reasons for spontaneous abortion are diverse and most likely include both genetic and environmental factors. Illicit drugs, primarily cocaine, are among the environmental factors implicated in spontaneous abortion. Ness and colleagues performed a case-control study of the influence of cocaine use and cigarette smoking on pregnancy outcome.
The study included 970 inner-city adolescents and women who presented to an urban emergency department for a variety of reasons. Urine pregnancy tests were used to confirm pregnancy, and the patient's report of her last menstrual period was used to estimate gestational age. Women were excluded from the study if their last normal menstrual period had been more than 22 weeks previously or within the past 28 days.
A 45-minute baseline interview was conducted to obtain information about cocaine, marijuana, alcohol and tobacco use. Blood, urine and hair samples were assessed for the presence of the major metabolites of cocaine, marijuana, amphetamines, opiates and nicotine. Follow-up telephone interviews were conducted at 16 and 22 weeks' gestation to determine the status of the pregnancy. A spontaneous abortion was defined as a pregnancy loss before 22 weeks' gestation. This loss was confirmed by pelvic examination, ultrasound examination and serial measurement of the serum human chorionic gonadotropin level.
The mean duration of pregnancy was 10 weeks at the time of entry into the study. Spontaneous abortion occurred in 400 women, and the remaining 570 were pregnant after 22 weeks' gestation. Hair analysis in the women who had a spontaneous abortion demonstrated that 28.9 percent had used cocaine, compared with 20.5 percent of those who did not have a spontaneous abortion. Urine cotinine was detected in 34.6 percent of the group with spontaneous abortion, compared with 21.8 percent of those who did not have a spontaneous abortion. Evidence of both cocaine and nicotine use was independently associated with a risk of spontaneous abortion. Calculated risk estimates demonstrated that cocaine and cigarette smoking accounted for 8 percent and 16 percent, respectively, of the spontaneous abortions. Marijuana and alcohol use did not independently relate to a risk of spontaneous abortion. No dose-response relationship was found between the amount of cocaine in the hair sample and the risk of spontaneous abortion.
The authors conclude that cocaine use and cigarette smoking in early pregnancy contribute to the occurrence of spontaneous abortion. The results suggest that cigarette smoking and cocaine use are independently associated with an increased risk of spontaneous abortion.
JEFFREY T. KIRCHNER, D.O.
Ness RA, et al. Cocaine and tobacco use and the risk of spontaneous abortion. N Engl J Med February 4, 1999; 340:333-9.
Effectiveness of Zafirlukast as Monotherapy for Severe Asthma
The treatment recommendations of the National Asthma Education and Prevention Program (NAEPP) are based on disease severity. The four categories of disease severity are mild intermittent, mild persistent, moderate persistent and severe persistent asthma. The recommended therapies for severe persistent asthma include an anti-inflammatory agent (i.e., a high-dose inhaled corticosteroid), a long-acting bronchodilator (typically a beta2 agonist) and oral corticosteroids. The leukotriene receptor antagonists are recommended as an alternative to inhaled corticosteroids in patients with mild to moderate persistent asthma, but experience with their use in patients with severe disease remains limited. Kemp and colleagues evaluated data on the efficacy of the leukotriene receptor antagonist zafirlukast in patients with severe persistent asthma.
The authors analyzed pooled data from four randomized, double-blind, placebo-controlled trials of zafirlukast in patients with asthma. These patients had never received corticosteroids. The authors identified a subset of 261 patients who at the time of the clinical trials were classified as having mild to moderate asthma (forced expiratory volume in one second [FEV1] of less than 60 percent of the predicted value). However, since those four studies were conducted, the NAEPP classification of disease severity changed. With the current classification system, patients such as these, with an FEV1 of less than 60 percent of predicted, are considered to have severe persistent asthma.
All of the 261 patients had an FEV1 of less than 60 percent of predicted but an increase of at least 15 percent in the FEV1 after inhalation of a bronchodilator. Each of the four studies lasted 13 weeks and were of a similar design. The treated patients received 20 mg of zafirlukast twice daily. The use of a beta agonist was allowed on an as-needed basis. During the initial screening and treatment, patients kept a record of their daily peak expiratory flow rates, asthma symptom scores and beta agonist use. At the beginning of the studies, the average FEV1 was 53 percent of predicted, the mean number of puffs per day of a beta agonist was six, and patients experienced four to five asthma-related nighttime awakenings per week.
Pooled data revealed that 64 percent of the patients who used zafirlukast had a 10 percent or greater increase in FEV1, compared with 50 percent of the patients in the placebo group. In addition, pulmonary function deterioration occurred in 21 percent of the patients in the zafirlukast group but in 35 percent of the patients in the placebo group. More importantly, the treatment group had a 26 percent decrease in daytime asthma symptom scores, a 27 percent decrease in nighttime awakenings, a 24 percent decrease in mornings with asthma symptoms and a 26 percent decrease in the use of a beta agonist. In addition, among patients with daily peak flow variability of more than 20 percent, the zafirlukast group had significant increases in both morning and evening peak expiratory flow rates compared with the placebo group.
The authors conclude that zafirlukast offers significant benefit, even as monotherapy, in patients with severe persistent asthma. Because the number and severity of adverse events did not differ in the treatment and placebo groups, this leukotriene receptor antagonist also appears to be a safe therapy. Additional studies are needed to evaluate this class of medication for use in combination with inhaled corticosteroids or other anti-inflammatory agents.
JEFFREY T. KIRCHNER, D.O.
Kemp JP, et al. Therapeutic effect of zafirlukast as monotherapy in steroid-naive patients with severe persistent asthma. Chest February 1999;115:336-42.
AHA Statement on Antioxidants and CoronaryDisease Prevention
Recent developments in understanding the process of atherosclerosis have led to the consideration that antioxidants may play a role in primary or secondary prevention. Specifically, antioxidants have been proposed as inhibitors of atherogenic and thrombotic events in the coronary arterial wall. Vitamin C, vitamin E and beta carotene are the dietary antioxidants that have received the most attention. Tribble, for the Nutrition Committee of the American Heart Association, reviewed evidence concerning the role of dietary antioxidants in coronary disease prevention and pointed out issues that need to be resolved before prophylactic use of antioxidants can be recommended.
The author states that support for the importance of dietary antioxidants in the prevention of coronary heart disease has mostly come from observational studies. In cohort and case-control studies, increased antioxidant intake was associated with a reduced risk of major coronary disease. The largest of these cohort studies was the Nurses' Health Study, in which 85,000 participants were followed for up to eight years. The risk of coronary disease was lowest in women with a vitamin E intake achievable only by supplementation. This study was reported in 1993.
In another study, a lower risk of major coronary events was reported in men who had a high intake of beta carotene. Subgroup analyses, however, revealed that this relationship was only significant in current and former smokers. A relationship between vitamin C intake and disease risk has not been reported in observational studies.
Direct experimental evidence that antioxidants prevent coronary disease is lacking. For example, no evidence of a benefit from beta carotene on cardiovascular disease was observed in the Physicians' Health Study, which involved 22,000 American male physicians. Similarly, the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study evaluated the effects of 50 IU of vitamin E, 20 mg of beta carotene or both, but did not demonstrate any reduction in the risk of lung cancer or major coronary events with the use of these antioxidants.
The author states that the results of secondary prevention trials have been more supportive of the potential benefits of antioxidants. For example, the Cambridge Heart Antioxidant Study showed a reduction in the risk of cardiovascular events with high dosages (400 or 800 IU) of vitamin E. The combined results of the two dosage levels showed that the risk of myocardial infarction was reduced by 77 percent and the risk of all cardiovascular events by 47 percent.
The author concludes that evidence in support of the potential health benefits of dietary antioxidants is insufficient. Thus, a general recommendation for supplementation cannot be endorsed. According to the AHA, the most prudent and scientifically supportable recommendation for the general population is to consume a balanced diet with emphasis on antioxidant-rich fruits and vegetables and whole grains. Although diet alone may not provide the levels of vitamin E intake that have been associated with a lowest risk in a few observational studies, the absence of efficacy and safety data from randomized trials precludes the establishment of a population-wide recommendation for vitamin E supplementation. In the case of secondary prevention, the results from clinical trials of vitgamin E have been encouraging and, if further studies confirm these findings, consideration of the merits of vitamin E supplementation in individuals with cardiovascular disease would be warranted.
JAMES NUOVO, M.D.
Tribble DL. Antioxidant consumption and risk of coronary heart disease: emphasis on vitamin C, vitamin E, and beta-carotene. A statement for healthcare professionals from the American Heart Association. Circulation February 2, 1999;99:591-5.
Low Doses of Mifepristone for Emergency Contraception
Studies comparing the effectiveness of the Yuzpe regimen with a single 600-mg dose of mifepristone for emergency contraception suggest that a single dose of mifepristone appears to be the better option. The Yuzpe regimen requires two doses of 100 mg each of ethinyl estradiol plus 500 mg of levonorgestrel given 12 hours apart within 72 hours of unprotected intercourse. Both regimens seem equally effective in preventing pregnancy, but women who took mifepristone reported less nausea and vomiting. Lower dosages of mifepristone may be equally effective in providing emergency contraception and should be considered, both to reduce cost and to follow the principle that patients should receive the lowest effective dosage of a drug. The Task Force on Postovulatory Methods of Fertility Regulation compared the effectiveness and side effects, including the timing of the next menstrual period, of three different dosages of mifepristone given within five days of unprotected intercourse.
Women eligible for this multinational randomized controlled trial had contacted one of 11 family planning clinics in order to prevent pregnancy. To be included in the study, women had to request contraception within 120 hours of a single act of unprotected intercourse and were required to have regular menstrual cycles, be willing to abstain from intercourse for the remainder of their cycle and have no contraindication to the medication. Women who met the inclusion criteria were randomized to receive either 600 mg, 50 mg or 10 mg of oral mifepristone. Once included in the study, the women were asked to refrain from intercourse or to use barrier methods of contraception until the onset of the next menses. In addition, they were asked to record all symptoms, particularly vaginal bleeding, and any further sexual activity. Follow-up was scheduled one week after onset of their next menses or two weeks after the date of their next anticipated menses, if bleeding did not occur. Pregnancy testing was performed at the follow-up visit in women whose menses had not started, and ultrasonography was used to confirm and date any suspected pregnancies.
A total of 1,717 women were enrolled in the study; data were collected for 1,684 women. Baseline characteristics were similar for the three groups. Approximately 57 percent of the women reported condom failure, and 41 percent reported that they had not used a contraceptive at the time of intercourse. Between 14 and 18 percent of each group reported a delay of more than 72 hours between coitus and treatment. Twenty-one women were pregnant after treatment, compared with an expected total of 136 without treatment. Of these, one woman was already pregnant at the time of treatment, and six others may have conceived two weeks after treatment. In women who abstained from intercourse for the remainder of the cycle, the pregnancy rates for all three treatment groups was 0.9 percent. Overall, mifepristone prevented 85 percent of the pregnancies that would have occurred without treatment. The only side effect of treatment was delayed onset of menses, which was found to be significantly related to the size of the dose. Delays of more than seven days occurred in 36 percent of those receiving 600 mg, 23 percent of those receiving 50 mg and 18 percent of those receiving 10 mg.
The authors conclude that the lowest dosage of mifepristone is as effective in preventing pregnancy as the larger dosages, making it a more affordable choice. The smaller dosage also resulted in the lowest incidence of side effects, particularly delay in onset of the next menses.
ANNE D. WALLING, M.D.
Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet February 27, 1999;353:697-702.
"Tips from Other Journals" are written by the medical editors of American Family Physician
Copyright © 1999 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.
