Tips from Other Journals
Loratadine and Fluticasone Nasal Spray: Added Benefit?
Standard treatment for seasonal allergic rhinitis consists of either an inhaled corticosteroid or a second-generation nonsedating antihistamine. Ratner and colleagues conducted a double-blind, placebo-controlled trial to evaluate whether concurrent administration of these medications provides any added benefit compared with monotherapy.
Patients who were at least 12 years old were included in the study if they had a positive skin-test reaction to mountain cedar, had the nasal mucosal appearance typical of seasonal allergic rhinitis and had a history of moderate to severe symptoms. Patients who had recently received antihistamines, corticosteroids or nasal decongestants were excluded from participation. Study subjects began a one-week to one-month run-in period and recorded their symptoms daily for the duration of the study. Patients were randomly assigned to receive one of four regimens: (1) two daily 50-µg sprays per nostril of fluticasone propionate aqueous nasal spray plus a placebo capsule; (2) a 10-mg loratadine capsule plus placebo nasal spray; (3) both treatment medications; or (4) a placebo spray and a placebo capsule. Use of other medications that could affect rhinitis symptoms was not permitted. Nasal symptoms and adverse events were recorded throughout the study, and each patient was examined for the development of nasal or oropharyngeal candidiasis. The patients also completed a disease-specific quality-of-life questionnaire.
A total of 569 patients completed the study. By the seventh day, the physicians rated nasal symptoms in the fluticasone nasal spray groups as significantly better than symptoms in the other groups. At 14 days, the treatment groups continued to have fewer symptoms than the placebo group.
Symptoms were most improved in the groups taking fluticasone. The patients in the combination therapy group rated their nasal symptoms (specifically, nasal blockage, nasal discharge and sneezing) most improved. The fluticasone and fluticasone-loratadine treatment regimens were more effective than the loratadine monotherapy regimen. Adverse effects were rare.
The authors conclude that patients with seasonal allergic rhinitis may be treated effectively with a 200-µg daily dosage of fluticasone propionate aqueous nasal spray. The addition of loratadine does not significantly benefit these patients.
GRACE BROOKE HUFFMAN, M.D.
Ratner PH, et al. A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis. J Fam Pract August 1998;47:118-25.
Diagnosing Osteitis Pubis: A Case Report and Review
Osteitis pubis is a disorder of the pubic symphysis. Andrews and Carek describe a case report and review the features and diagnosis of this disorder.
The differential diagnosis of pain in the pubic symphysis includes muscle strain, prostatitis, orchitis, arthritis, fracture and osteitis pubis. Other causes include ankylosing spondylitis, Reiter syndrome, urolithiasis and hyperparathyroidism. Osteitis pubis was first described in 1924 by a urologist who noted the condition in patients who had undergone suprapubic surgery. It has subsequently been diagnosed in athletes and in patients who have had urologic or gynecologic surgery.
There is some speculation that osteitis pubis may be caused by trauma or infection. However, radiographic evidence does not indicate avulsion or other trauma to the pubis. Some patients describe localized pain about one month after surgery, and these patients may be found to have infection with Pseudomonas aeruginosa (most commonly), Escherichia coli or Staphylococcus aureus. In some cases of infection the leukocyte count is normal, the erythrocyte sedimentation rate is only slightly increased and blood cultures are negative. Bone biopsy may be required to determine the organism involved.
Usually, osteitis pubis is considered to be an inflammatory condition. It is self-limited and occurs more often in men who are in their 20s or 30s. It may cause pain localized to the pubic, groin or abdominal areas. The patient may experience pain with activity. This pain may occur in the perineal, testicular, suprapubic or inguinal areas. Patients may also experience postejaculatory scrotal or perineal pain. Range of motion may be decreased in one or both hips.
Plain films of the pubis may be normal or may show sclerosis and irregular cortical margins. Radionuclide studies will show unilateral uptake of the pubic symphysis.
Osteitis pubis can be treated with rest, ice, physical therapy and nonsteroidal anti-inflammatory medications. After the initial treatment, efforts should be made to strengthen hip flexors and pelvic muscles. It generally takes about three to six months for patients to resume a premorbid functioning level. Osteitis pubis recurs in approximately 25 percent of patients.
GRACE BROOKE HUFFMAN, M.D.
Andrews SK, Carek PJ. Osteitis pubis: a diagnosis for the family physician. J Am Board Fam Pract July-August 1998;11:291-5.
Endometrial Cells on Pap Smear and Endometrial Cancer
Endometrial cancer is one of the more common gynecologic malignancies in the United States. Despite recent advances, approximately 6,000 deaths result from endometrial cancer each year. Several studies have suggested a correlation between endometrial cells (both normal and abnormal) on Papanicolaou smears and endometrial cancer, mainly in postmenopausal women. Kerpsack and associates conducted a study to evaluate a possible correlation between the presence of endometrial cells on Pap smear and significant endometrial pathology.
All Pap smears from a medical foundation patient population over a three-year period were reviewed. Of 119,000 Pap smears in the screening pool, 61 included endometrial cells. Nine patients were lost to follow-up and five had no further testing and were classified as of benign etiologies; the remaining patients received endometrial aspiration, endometrial curettage or hysterectomy for tissue confirmation. Thirty-one of the patients had benign endometrial cells on Pap smear. Five patients had atypical glandular cells of undeterminant significance suggestive of endometrial cells, 11 patients had atypical endometrial cells and four patients had adenocarcinoma. Forty-four patients were postmenopausal; 12 of these women were taking hormone replacement therapy. Twenty-four of the patients had abnormal vaginal bleeding. In the final analysis, 45 patients were found to have benign disease and seven patients had carcinoma. Two patients with endometrial cancer had benign endometrial cells on their Pap smears; the remainder had more advanced abnormalities. The majority of patients with endometrial cancer had abnormal vaginal bleeding.
The authors conclude that asymptomatic patients who have benign endometrial cells on Pap smear but no abnormal vaginal bleeding do not require further evaluation. However, even if the endometrial cells are described as benign, a patient with abnormal vaginal bleeding should receive further evaluation with dilatation and curettage.
KARL MILLER, M.D.
Kerpsack JT, et al. Correlation between endometrial cells on Papanicolaou smear and endometrial carcinoma. South Med J August 1998;91:749-52.
Review of Current Treatment Strategies in Heart Failure
The prevalence of heart failure is increasing in most developed countries because of aging populations. Older patients are also likely to have more concomitant diseases, complicating treatment. Recently, the goals of therapy have shifted from improving hemodynamic measurements to delaying death and improving the patient's quality of life. Cleland and associates reviewed treatment modalities for patients with heart failure and emphasized the importance of implementing treatment strategies proven effective in clinical trials into community practice.
Diuretics are the most popular form of treatment for heart failure, as they relieve symptoms of fluid overload, such as dyspnea and edema. Studies have shown that these symptoms recur in patients with moderate heart failure when diuretics are withdrawn or an angiotensin converting enzyme (ACE) inhibitor is substituted. Withdrawing diuretics for an extended period of time and substituting an ACE inhibitor may be appropriate in selected patients with mild heart failure, but more research is needed to clarify the optimal use of diuretics. Specifically, should diuretics be used regularly or intermittently, guided by weight gain and evidence of fluid retention? The development of new classes of diuretics and loop diuretics with high bioavailability may renew interest in the use of diuretic therapy for heart failure.
The effectiveness of digoxin therapy in the management of heart failure remains unclear. Findings from one study showed that, in standard dosages, digoxin appears to be safe and was associated with a modest reduction in hospital admissions. Standard dosages, however, may not achieve plasma concentrations in the generally accepted therapeutic range. The therapeutic range for digoxin is narrow, and increasing plasma concentrations are clearly linked to mortality.
The use of ACE inhibitors has been shown to effectively control symptoms, reduce hospital admission and lower the risk of myocardial infarction in patients with left ventricular systolic dysfunction. The benefit of ACE inhibitors has been shown to be dosage-related. Higher dosages appear to be more effective than lower dosages. Many patients with heart failure who should be receiving ACE inhibitors are not, and those who are may be receiving a dosage that is too low. More than one half of the patients with apparent heart failure have normal systolic function in the left ventricle, and the role of ACE inhibitors in these patients is unclear. Beta blockers have been shown to reduce morbidity and mortality in patients with heart failure. However, they can cause an initial exacerbation of heart failure, so they are not currently recommended for use in patients who have severe heart failure or New York Heart Association class IV heart failure. Beta blockers are also contraindicated in patients who have asthma, and their safety in patients older than 75 years who have heart failure has not been established. Beta blockers should be started at a low dosage and gradually titrated to effective levels.
Studies of older calcium-channel blockers showed no benefit in patients with heart failure. More recent studies of newer calcium channel blockers, especially those of felodipine and amlodipine, suggest symptomatic benefit. Other studies have suggested benefit when verapamil or diltiazem is used in conjunction with an ACE inhibitor. Much more research is needed to determine which subgroups of patients, if any, benefit from the use of calcium channel blockers in the management of heart failure related to left ventricular diastolic dysfunction.
The authors conclude that many agents are currently available, enabling physicians to tailor therapy for heart failure more appropriately for individual patients. Ongoing research should overcome many of the current uncertainties and ambiguities in treating this common condition.
ANNE D. WALLING, M.D.
Cleland JG, et al. Successes and failures of current treatment of heart failure. Lancet (Suppl 1) August 1998; 352:19-28.
Effect of Beta Blockers on Mortality Following MI
Long-term use of beta-adrenergic blockers has been shown to decrease mortality in patients who have sustained a myocardial infarction (MI). Despite evidence from several clinical trials, follow-up studies have shown that physicians prescribe these agents to only 30 to 50 percent of patients after a myocardial infarction. Physician reluctance to prescribe these agents may be associated with patient characteristics that are presumed to be contraindications, such as older age, poor left ventricular function, a history of chronic obstructive pulmonary disease (COPD) and the use of diuretic drugs. Gottlieb and colleagues examined data from the Cooperative Cardiovascular Project to identify which patients benefit from treatment with beta blockers by comparing risk factors and mortality rates in high- and low-risk patients.
The Cooperative Cardiovascular Project is a program designed to evaluate the care of Medicare patients who have had a myocardial infarction. Its primary intent is to evaluate the relationship between treatment and outcomes. The medical records of more than 200,000 patients with myocardial infarction who had been prescribed a beta blocker at the time of hospital discharge were included in the study. Most of the patients were older than 65 years. Data on ejection fraction and serum creatinine levels were available for most patients. Mortality rates of patients who received a beta blocker were compared with those who did not, based on a time-to-event analysis. Approximately 95 percent of the patients were followed for two years.
Only 34 percent of the patients in the study group received beta blockers at the time of hospital discharge; very elderly patients, black patients and patients considered to be the sickest were the least likely to receive this therapy. In addition, patients who had low ejection fractions, a history of congestive heart failure, COPD, elevated serum creatinine levels or type 1 diabetes mellitus were also less likely to receive beta blockers. Patients undergoing more aggressive treatments, such as thrombolysis or angioplasty, were more likely to receive beta blocker therapy. Overall, patients who received beta-blocker therapy had fewer risk factors for mortality, including younger age, better left ventricular ejection fraction and fewer coexisting illnesses, than those who did not receive beta-blocker therapy.
Evaluation of individual subgroups revealed that treatment with beta blockers was associated with a reduction in mortality of 40 percent in patients who had sustained a myocardial infarction but had no other complications. A reduction in mortality of 40 percent occurred in patients with COPD or nonQ-wave infarctions. A reduction of 36 percent occurred in patients with diabetes mellitus. However, treatment with beta blockers resulted in a reduction in mortality of only 28 percent in black patients; in patients older than 80 years and patients with a left ventricular ejection fraction below 20 percent, mortality rates decreased only 32 percent.
The authors conclude that mortality from myocardial infarction was reduced in every subgroup of patients who received beta blockers. However, as previous studies also reported, these drugs are widely underused. Had beta blockers been prescribed more widely, more than 19,000 deaths could have been prevented in this cohort of over 200,000 patients. In addition to otherwise healthy patients, those with heart failure, pulmonary disease, advanced age and nonQ-wave infarctions may benefit from therapy with beta blockers after a myocardial infarction.
JEFFREY T. KIRCHNER, D.O.
Gottlieb SS, et al. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med August 1998;339:489-97.
A Program of Foot Care to Reduce Diabetes-Related Amputations
Despite evidence that foot care can prevent amputations, this continues to be a commonly neglected aspect of management in patients with diabetes. Rith-Najarian and colleagues conducted a prospective study to evaluate the impact of foot care guidelines for patients with diabetes at an American Indian health service clinic.
The study, which began in 1986 and continued through 1996, was divided into three phases. The first phase, from 1986 to 1989, was an observation period to determine the types of foot care provided to patients with diabetes. This was followed by the second phase (1990 to 1993), during which patients were screened for foot problems, and high-risk patients received foot-care education and protective footwear. High-risk patients were considered those who demonstrated insensitivity to a 10-g monofilament examination, had a foot deformity or had a history of foot ulcers or prior amputation.
The final phase of the study, conducted from 1994 to 1996, included the implementation of systematic screening, diagnostic and treatment guidelines for diabetic foot management. These guidelines contained specific algorithms for foot care, treatment options and schedules for follow-up. The practice guidelines are available at the Journal of Family Practice Web site (http://jfp.denver.co.us; click on "supplemental material").
The first phase of the study revealed no systematic method of diabetic foot management. Similarly, in the second phase, there was no consistent approach to foot care or ulcer assessment. After the staged diabetes management guidelines were developed, changes were implemented at the Indian health service clinic. A foot care team was organized, flow sheets based on the guidelines were developed, and standardized management strategies were executed.
A total of 639 patients were included in the study. Patients did not significantly differ in age, sex or duration of diabetes. The average annual incidence of amputation during the standard care phase (phase one) was 29 per 1,000 patient-years. In the second phase, the average annual incidence was 21 per 1,000. The average annual incidence of amputations dropped to 15 per 1,000 in the final phase of the study. Among patients with intact limbs, the rate of first amputation was reduced by 71 percent between the first and third phases.
The authors conclude that screening, along with some basic interventions such as patient education and protective footwear, reduced lower extremity amputation rates by 28 percent compared with the rate during standard care. After the staged diabetes management system was implemented, a 48 percent reduction in lower extremity amputations was achieved. The authors recommend the staged diabetes management system for reducing the rate of amputation in patients with diabetes. Similar methods may also be useful for reducing other complications and improving outcomes in patients with diabetes.
GRACE BROOKE HUFFMAN, M.D.
Rith-Najarian S, et al. Reducing lower-extremity amputations due to diabetes. Application of the staged diabetes management approach in a primary care setting. J Fam Pract August 1998;47:127-32.
White Coat Hypertension: Not a Benign Condition
Patients whose blood pressure readings are elevated when measured in a clinical setting but are within normal range in nonmedical environments are considered to have "white coat," or transient, hypertension. Although it traditionally has been regarded as a benign condition, recent studies have revealed correlations between white coat hypertension and unfavorable risk factors in young adults. Muscholl and colleagues studied left ventricular structure and function in patients with white coat hypertension.
During the community-based study, data were collected, and echocardiographic studies were performed on 845 men and 832 women who were 25 to 74 years of age. Repeated blood pressure readings were taken by technicians, using standardized protocols. The technicians did not wear white coats, and the environment was structured to appear informal and nonclinical. Patients were not told their blood pressure levels until three readings had been taken. Within 60 minutes of the technicians' readings, blood pressure levels were measured by a physician wearing a white coat who was introduced as a cardiologist. Echocardiography was performed immediately before the blood pressure measurement was taken by the physician.
Patients meeting the criteria for white coat hypertension had blood pressure readings that were normal (less than 140/90 mm Hg) when taken by a technician but reached hypertensive levels (160/95 mm Hg or higher) when recorded by a physician. The prevalence of white coat hypertension was higher in men (10.9 percent) than in women (8.2 percent); overall, 10 percent of the study population displayed the condition.
Even after adjusting for age, sex and body mass index, patients with white coat hypertension had significantly increased left ventricular mass indexes. The increased cardiac mass was due to increased thickness of the posterior wall and the septum of the left ventricle. Patients with white coat hypertension did not show abnormal systolic function of the left ventricle and had no abnormalities of diastolic filling or left atrial size.
The authors conclude that white coat hypertension is a common condition that can no longer be dismissed as benign or as having no consequence. They believe the finding is related to an increased risk of left ventricular hypertrophy and cardiac remodeling. They advocate more intense monitoring and control of cardiovascular risk factors in adults found to have elevated blood pressure readings exclusively in clinical settings.
ANNE D. WALLING, M.D.
Muscholl MW, et al. Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey. BMJ August 29, 1998;317:565-70.
Should Blood Screening Be Routine for Vaginal Delivery?
Women who are admitted to a hospital in anticipation of a vaginal delivery frequently undergo blood typing and screening because of the remote risk that they may require a blood transfusion. Ransom and colleagues conducted a three-year retrospective review to evaluate the cost effectiveness of routine blood typing and screening in women admitted to the hospital for expected vaginal delivery.
Most of the patients included in the study were black (76 percent), and more than 50 percent were at high risk of poor obstetric outcome for medical or social reasons. Overall, 76 of the 16,291 women (0.46 percent) delivering vaginally received blood transfusions; the need for an urgent transfusion was 2.5 per 10,000 deliveries. All but four patients who were urgently transfused had at least one of four risk factors: anemia at admission, previous cesarean delivery, placental abruption or history of blood transfusion.
The authors estimate that limiting blood typing and screening on admission to women who have at least one risk factor for blood transfusion would reduce the number of tests by 70 percent. Such selective testing would have resulted in a savings for the hospital of approximately $600,000 during the three-year study period.
The authors advocate a selective policy of laboratory testing for potential blood transfusion in patients admitted for probable vaginal delivery. Eliminating routine type and screen testing nationwide could amount to a savings of $120 million per year. In the rare circumstance that an urgent blood transfusion is needed, O-negative blood could be given until a type and crossmatch determination is made. O-negative blood is available within 10 minutes at the study hospital, and matched blood is available in approximately 40 minutes. Because study results did not show that routine testing and screening provided any significant improvement in patient care, the authors call for its elimination from clinical pathways for patients with no risk factors.
ANNE D. WALLING, M.D.
Ransom SB, et al. The cost-effectiveness of routine type and screen admission testing for expected vaginal delivery. Obstet Gynecol October 1998;92:493-5.
Alternatives for Intrapartum Prophylaxis of Group B Strep
Prophylactic use of ampicillin and penicillin G in pregnant women has been shown to be effective in preventing vertical transmission of group B streptococcal infection. In pregnant women who are allergic to penicillin, clindamycin and erythromycin have been recommended as acceptable alternatives. However, in the past 10 years, severe neonatal infections have been reported, despite documented prophylaxis with clindamycin and erythromycin. Pearlman and colleagues conducted a study to determine the frequency of in vitro resistance of group B streptococci to these penicillin alternatives and to define ways of treating pregnant women who report penicillin allergy.
Clinical specimens of group B streptococci were obtained from genitourinary sites by cotton swab in 100 patients to assess in vitro rates of resistance to clindamycin, erythromycin, penicillin G, vancomycin and cefazolin. Labor and delivery records for all women who were screened for a history of penicillin allergy and who delivered at a university medical center during a four-month period were also collected.
All of the 100 clinical isolates of group B streptococci obtained were sensitive to penicillin G, cefazolin and vancomycin. Thirteen (16 percent) of the 82 isolates tested were resistant to erythromycin, and 15 percent were resistant to clindamycin. Resistance to more than one agent was also observed. Of the 13 erythromycin-resistant isolates, resistance to clindamycin was present in eight (62 percent), and nine out of the 10 clindamycin-resistant isolates (90 percent) were also resistant to erythromycin. Penicillin allergy was cited by 111 of the 963 women studied (12 percent). Of these, 14 reported severe reactions, 13 reported rashes, and six reported nausea or diarrhea. Seventy percent of the women who reported penicillin allergy had no specific observable manifestations during the study.
The authors conclude that the significant levels of resistance to clindamycin and erythromycin found in this study could explain the failure of current regimens to prevent group B streptococcal infection in pregnant women reporting penicillin allergies. The authors recommend more focused questioning when obtaining a history of penicillin allergies or using skin testing to verify reported penicillin allergy, since many women may be denied effective prophylaxis with penicillin because of their nebulous report of a previous adverse effect. For most patients in this study who reported penicillin allergies, an acute hypersensitivity reaction that contraindicated penicillin use could not be established.
ANNE D. WALLING, M.D.
Pearlman MD, et al. Frequent resistance of clinical group B streptococci isolates to clindamycin and erythromycin. Obstet Gynecol August 1998;92:258-61.
Underdosage of ACE Inhibitors for Congestive Heart Failure
Therapy with angiotensin converting enzyme (ACE) inhibitors has been shown to reduce the rate of hospitalization in patients with congestive heart failure (CHF), and these medications are recommended as first-line agents by the Agency for Health Care Policy and Research (AHCPR). Recent surveys, however, show that these agents are prescribed in only 40 to 70 percent of patients with CHF. Moreover, data indicate that daily dosages are often below the recommended equivalent of 20 mg or more of enalapril. Luzier and associates conducted a retrospective study to investigate whether the dosing recommendations of the AHCPR are effective in routine clinical practice and to test the impact of these drugs on the rate of rehospitalization in patients with CHF.
A total of 314 patients admitted at least twice during a 36-month period because of CHF were included in the study. For the purposes of analysis, ACE inhibitor dosages were converted to enalapril-equivalent dosages according to target daily doses recommended in the AHCPR guidelines. These dosages were 20 mg of enalapril, 150 mg of captopril and 20 mg of lisinopril daily.
Most of the patients received combination therapy, with nearly one half receiving the full regimen of a diuretic, digoxin and an ACE inhibitor. However, ACE inhibitor doses were consistent with the AHCPR guidelines in only 45 of 209 patients (22 percent) receiving an ACE inhibitor or 45 of 314 patients (14 percent) overall.
Diuretic therapy was found to be associated with a decrease in time to readmission, whereas digoxin had no effect. The ACE inhibitor dose was a significant covariant of the 90-day readmission rate. Daily dosages of 2.5 mg and 5 mg of enalapril were not associated with a significant reduction in the relative risk of readmission. In contrast, 10 mg of enalapril reduced the relative risk of readmission to 0.55, and 20 mg of enalapril further reduced the relative risk of readmission to 0.44. This dose-response relationship appeared to be unrelated to the severity of CHF.
A clear dose-response relationship was found, with increasing ACE inhibitor doses lowering the probability of readmission. Using the modeled function, it was possible to estimate the maximum ACE inhibitor effect and to identify the extrapolated maximum benefit that could be derived. Achievement of 90 to 95 percent of the theoretic maximum benefit would require an enalapril dosage of 100 to 200 mg daily.
The authors conclude that ACE inhibitor dosages higher than those currently in general use are required to achieve optimal effect in patients with CHF. At a minimum, clinicians should prescribe the dosages recommended by the AHCPR for the management of CHF.
RICHARD SADOVSKY, M.D.
Luzier AB, et al. Impact of angiotensin-converting enzyme inhibitor underdosing on rehospitalization rates in congestive heart failure. Am J Cardiol August 15, 1998;82: 465-9.
EDITOR'S NOTE: ACE inhibitors change the balance between the properties of angiotensin II and bradykinin, causing vasodilation and natriuresis. Metabolism of other vasoactive substances may also be altered. This decrease in systemic vascular resistance occurs without an increase in the heart rate. ACE inhibitors have been shown to decrease mortality in patients with CHF and in patients with left ventricular dysfunction after myocardial infarction and to delay progression of diabetic nephropathy in patients with diabetes. Adequate dosage is important to achieve the desired effects in these populations. Future research may determine that ACE inhibitor dosages even larger than those currently recommended may decrease mortality and morbidity in specific populations.
R.S.
Drainage of Large Pericardial Effusion Without Tamponade?
The optimal treatment of large pericardial effusions remains controversial. Some physicians advocate routine pericardial drainage in all patients, while others argue that these procedures offer no benefit unless cardiac tamponade is present. Mercé and associates analyzed patient records to identify any diagnostic or therapeutic benefit to draining a large pericardial effusion as part of routine initial treatment in patients with pericardial effusion without cardiac tamponade.
Records of all patients who were treated at a hospital in Spain for large pericardial effusion without cardiac tamponade over a six-year period were reviewed. A large effusion was defined as an echo-free space during diastole of at least 20 mm, as recorded on echocardiogram. Patients with chronic effusions and those who were suspected of having a purulent effusion were excluded from the study.
The diagnostic yield of pericardiocentesis or pericardial biopsy was evaluated. Hospital protocol was followed for the management of patients with acute pericardial disease; pericardiocentesis was performed on patients who had a cardiac tamponade, a suspected purulent pericarditis or a chronic large effusion that persisted for at least three months. Surgical drainage and pericardial biopsy were performed in patients whose tamponade had relapsed after initial pericardiocentesis and in those whose clinical illness persisted three weeks after hospital admission.
Seventy-one patients with large pericardial effusions were included in the analysis. Of the 13 patients who met the study protocol criteria for pericardial drainage, only one was diagnosed following the procedure. In the 58 patients who did not meet the protocol criteria, 13 underwent a pericardial procedure anyway. Ten patients underwent one of the procedures for medical reasons; three underwent a procedure for diagnostic reasons. However, no other specific diagnoses were obtained.
A total of 24 patients underwent pericardiocentesis and in only one was a specific diagnosis obtained. Of the two pericardiotomies performed, only one yielded new information, bringing the total diagnostic yield of pericardiocentesis and surgical biopsy to 7 percent. Follow-up data were obtained in 68 of the 71 patients (95 percent) for a median of 10 months. During follow-up, five patients underwent pericardial procedures, but none of these led to new diagnoses. The effusions resolved within weeks without any intervention in 38 of the 40 patients in whom pericardial drainage was not performed and who were evaluated during follow-up.
The authors conclude that the use of pericardial procedures does not effectively increase diagnostic yield or improve resolution of large pleural effusions. Routine drainage is not warranted in the initial management of patients with large pericardial effusions, unless cardiac tamponade is present or purulent effusion is suspected.
GRACE BROOKE HUFFMAN, M.D.
Mercé J, et al. Should pericardial drainage be performed routinely in patients who have a large pericardial effusion without tamponade? Am J Med August 1998;105:106-9.
Valaciclovir for Suppression of Recurrent Genital Herpes
Infection with genital herpes simplex virus (HSV) causes significant morbidity for millions of infected persons. Without therapy, more than 90 percent of patients experience clinical recurrences, but a decade of experience has demonstrated that daily suppressive therapy with acyclovir, in a dosage of 400 mg twice daily, is effective and is well-tolerated by patients. Reitano and colleagues conducted a placebo-controlled study to compare this regimen with a range of once-daily dosages of valaciclovir in immunocompetent adults.
A total of 1,479 patients with documented HSV infection were selected for the study. The patients must have had at least six clinical episodes of HSV per year and been free of significant hepatic or renal disease. After screening, patients were randomly assigned to one of six treatment groups. Treatment consisted of valaciclovir: 250 mg once daily, 500 mg daily, 250 mg twice daily or 1 g daily; acyclovir: 400 mg twice daily; or placebo. Treatment continued for one year, with patients returning to the clinic monthly. Patients were instructed to contact the clinic within 24 hours of onset of a clinical recurrence of HSV infection. Hematology and clinical chemistry parameters were monitored at enrollment, at six months and after one year of therapy. Plasma acyclovir levels were determined at three, six, nine and 12 months. Patients kept diaries throughout the study to monitor adverse effects, clinical recurrences and use of other medications.
The full protocol was completed by 1,050 patients (71 percent). The most common reason for not completing the protocol was loss to follow-up (9.2 percent). Five percent of patients reported adverse experiences as a reason for discontinuing the study. The proportions of recurrence-free patients at one year were 50 percent in the group taking 250 mg of valaciclovir twice daily; 48 percent in the group taking 1 g of valaciclovir once daily; 49 percent in the group taking 400 mg of acyclovir twice daily; and 40 percent in the group taking 500 mg of valaciclovir once daily. In patients who were taking 250 mg of valaciclovir once daily, the proportion of nonrecurrence fell to 22 percent. In the group taking placebo, the recurrence-free rate was 5 percent. Three regimens, valaciclovir at 250 mg twice daily, valaciclovir at 1 g daily and acyclovir at 400 mg twice daily, reduced the recurrence rate by 78 to 79 percent. Valaciclovir in a dosage of 500 mg once daily was associated with a reduction of 71 percent. The 250-mg daily dosage of valaciclovir reduced recurrence by 54 percent compared with placebo. The safety profiles of all treatments were comparable.
After an analysis of subgroups, the authors concluded that valaciclovir, in a dosage of 500 mg once daily, effectively treated patients with a history of up to 10 HSV recurrences per year. In patients with a history of 10 or more recurrences per year, the most effective daily regimens were valaciclovir in a dosage of 1 g daily or 250 mg twice daily, and acyclovir in a dosage of 400 mg twice daily.
ANNE D. WALLING, M.D.
Reitano M, et al. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose rangefinding study. J Infect Dis September 1998;178:603-10.
Efficacy of Beta Blockers in Elderly Patients with MI
Beta blockers are known to be useful for secondary prevention in patients who have had an acute myocardial infarction. However, studies suggest this class of medication is underutilized, especially in older patients. Krumholz and colleagues in the National Cooperative Cardiovascular Project evaluated prescribing patterns and the effects of beta blockers in elderly patients with myocardial infarction.
Patients at least 65 years of age who had a primary discharge diagnosis of acute myocardial infarction were included in the study. Exclusion criteria included bradycardia, hypotension, high-grade atrioventricular block, asthma, chronic lung disease, heart failure and documented intolerance to beta blockers.
Information was abstracted from medical records. The main outcomes measured included frequency of beta-blocker therapy and mortality within one year of hospital discharge. Demographic information, length of stay and clinical status were also recorded.
The records of 115,015 patients with a principle diagnosis of acute myocardial infarction were reviewed, and 45,308 of these patients were considered candidates for beta-blocker therapy. Only 50 percent of the candidates were prescribed this therapy. Those who were prescribed discharge medicines (particularly calcium channel blockers) were much less likely to be given beta blockers.
Physician specialty was also found to be a factor in whether a patient received beta blockers. Family physicians were less likely than cardiologists and internists to prescribe beta-blocker therapy. There were 36,795 patients who were not receiving beta-blocker therapy on admission to the hospital; 43.5 percent of these patients started this therapy before discharge.
The one-year mortality rate was significantly less in patients receiving beta blockers (7.7 percent) than in those not receiving beta-blocker therapy (12.6 percent). When adjustment was made for all variables, beta-blocker therapy was still associated with a 14 percent lower mortality risk. The adjusted relative risk was 0.83 for men and 0.89 for women.
The authors confirm that beta blockers are underutilized in the elderly population. They conclude that care of patients could be improved with more attention to prescribing beta blockers after myocardial infarction to elderly patients without contraindications to this treatment.
GRACE BROOKE HUFFMAN, M.D.
Krumholz HM, et al. National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction. National Cooperative Cardiovascular Project. JAMA August 19, 1998;280:623-9.
Use of Opioids for the Chronic Pain of Rheumatic Diseases
The use of opioids in the treatment of chronic musculoskeletal pain is controversial. Concerns about efficacy, toxicity and the development of tolerance, dependence, addiction or abuse have been raised. Physicians may also be concerned about scrutiny by regulatory agencies when prescribing long-term opioid medications. Recent studies of the use of opioids in cancer patients suggest that there is a place for these medications in the treatment of chronic pain. Ytterberg and associates examined efficacy, toxicity, tolerance, addiction and abuse behaviors in patients who received opioid therapy for pain associated with chronic rheumatic disease.
Patients at a rheumatology clinic who had received at least one prescription for opioid therapy were enrolled in the study. Data were obtained from computerized pharmacy records, medical record reviews and patient interviews. Patients who did not receive opioids served as the control group. The 290 patients who received opioids were divided into two groups: long-term users (137 patients) and short-term users (153 patients). Long-term use was defined as opioid therapy lasting for at least three consecutive months; short-term use was defined as opioid therapy lasting fewer than three consecutive months. Dosage escalation was defined as an increase of two or more equivalents of 30 mg of codeine per day. Patients were asked to rate their pain on a scale of zero to 10, before and after a dose of their pain medication.
No significant demographic differences were noted between patients in the short-term, long-term or control groups. Opioid use in both the long-term and short-term groups had a significant impact on pain reduction. Over 85 percent of patients in these groups experienced reduction of pain severity of at least 30 percent. Thirty-eight percent of these patients reported side effects from opioid use, but very few patients stopped taking the opioid because of these side effects. No significant escalation of opioid dosage over time was reported in the long-term treatment group. Some patients did escalate their dosage, but 97 percent of the time this escalation was related to an increase in the severity of their pain. Only four patients were found to have developed tolerance to the drug and behaviors consistent with abuse. Seventy-three of the 133 patients receiving long-term therapy reported not taking medication on days with less pain because they were afraid of becoming addicted or dependent.
The authors conclude that their findings support the use of both long-term and short-term use of opioids in the treatment of musculoskeletal pain. Concerns about tolerance and escalation of opioid dosage were not supported by the study. Most patients participating in the study used opioids in an appropriate manner, escalating the dosage when needed and then returning to their baseline dosage. The authors state that it is no longer appropriate to withhold opioid treatment from patients with chronic pain from rheumatic disease because of doubts or concerns about opioid efficacy, tolerance, toxicity and abuse or addiction.
KARL MILLER, M.D.
Ytterberg SR, et al. Codeine and oxycodone use in patients with chronic rheumatic disease pain. Arthritis Rheum September 1998;41:1603-12.
Postmenopausal Women With CHD: What's the Role of HRT?
Estrogen replacement therapy has been shown to reduce the risk of coronary heart disease (CHD) in women, especially in women who have a history of this disease. Hulley and colleagues report the results of the Heart and Estrogen/progestin Replacement Study (HERS), which evaluated postmenopausal women with heart disease to see if therapy with estrogen plus progestin lowered the risk of events associated with coronary heart disease.
Postmenopausal women younger than 80 years who had established coronary heart disease were randomized to receive either conjugated equine estrogen plus progestin or a placebo daily. Women were excluded from the study if they had had an event associated with their coronary disease in the previous six months.
Baseline physical examination included a breast examination, Papanicolaou smear, endometrial evaluation, mammogram and an electrocardiogram. A lipid profile was also performed. Patients were examined every four months. After one year, many of the baseline studies were repeated. Outcome measures were nonfatal myocardial infarction or death as the result of coronary heart disease.
Of the 2,763 women enrolled in the study, 1,380 received hormone replacement therapy (HRT) and 1,383 received placebo. The average length of follow-up was 4.1 years. More women in the treatment group experienced events associated with coronary heart disease in the first year of treatment, although this early increase did not continue throughout the follow-up period. Overall, coronary heart disease events occurred in 172 women in the treatment group and in 176 women in the control group. These differences were not statistically significant. However, women in the treatment group did experience significant increases in the risk of gallbladder disease and venous thromboembolism.
The authors conclude that the use of estrogen-progestin replacement therapy in postmenopausal women for secondary prevention of coronary heart disease is unwarranted. However, women who are already receiving therapy should continue it, as the reduction of events associated with heart disease is favorably affected after several years of treatment. In a related editorial, Petitti underscores the efficacy of estrogen replacement therapy for bone and menopausal symptoms and stresses that no woman, even those with coronary heart disease, should stop hormone replacement therapy solely on the basis of the HERS study results.
GRACE BROOKE HUFFMAN, M.D.
Hulley S, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA August 19, 1998;280: 605-13, and Petitti DB. Hormone replacement therapy and heart disease prevention. Experimentation trumps observation [Editorial]. JAMA August 19, 1998;280:650-1.
"Tips from Other Journals" are written by the medical editors of American Family Physician.
Copyright © 1999 by the American Academy of Family Physicians.
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