Editorials - October 15, 2000 - American Family Physician

Editorials

Why Aren't We Using Beta Blockers After Acute MI?

AMY S. WEICHEL, D.O.
Georgetown University Medical Center
Washington, D.C.

See article in this issue.

In this issue of American Family Physician, Howard and Ellerbeck¹ discuss the underutilization of therapy with beta blockers after acute myocardial infarction (MI). That beta blockers are useful after acute MI is certainly not a new concept in medicine; the evidence that beta blockers significantly reduce mortality after acute MI was produced in the Beta-Blocker Heart Attack Trial² (BHAT) in the early 1980s.

If the evidence has been around for nearly 20 years, why are so many practitioners not using beta-blocker therapy in patients who have had an MI? This is not an easy question to answer. As physicians, we are inundated with new literature, new medications and new technology, and this information overload can be quite overwhelming. However, it has been shown repeatedly that beta blockers decrease mortality after acute MI. How many ways can it be said?

How many times do we have to hear the evidence before we change our practice habits? Therapeutic trials are performed with the idea that favorable outcomes will cause health practitioners to change their practice habits. This is an easy concept: if something helps, we should do it, and if something does not help, we should not do it. The concept does not appear to be that easy in practice, however. If matters were clear-cut, for the past 20 years eligible patients would have received beta blockers after acute MI, and the evidence does not show that this is the case.³

What will it take to get us to change our ways? Studies have evaluated which interventions are the most helpful in trying to get physicians to put new evidence into practice. Obviously, though, we all learn in different ways.

One study⁴ attempted to categorize interventions according to their effectiveness in promoting behavior changes in physicians. Certain interventions were consistently effective in promoting change. These included educational outreach visits, computerized or manual reminders, interactive educational workshops and multifaceted interventions (combining two or more of the following: reminders, local consensus processes, audit and feedback reminders and marketing). The interventions with variable effectiveness included use of local opinion leaders and patient-mediated interventions. Audit and feedback and local consensus processes alone also showed variable effectiveness. The interventions that were shown to have little or no effect included educational materials and didactic educational meetings.

So where does that leave us? Many physicians receive their new information in just those ways that were shown to be less helpful: educational materials (such as clinical practice guidelines, audiovisual materials and electronic publications) and didactic educational meetings (such as lectures).⁵ I see what the studies show; however, I know that for me, repetition is the key to learning, and perhaps others learn this way too. So, for what it is worth, let me stress yet again: beta blockers significantly reduce mortality after acute myocardial infarction. Let's put this evidence into practice.

Dr. Weichel is an instructor in the Department of Family Medicine at Georgetown University Medical Center, Washington, D.C.

Address correspondence to Amy S. Weichel, D.O., Georgetown University Medical Center, 3800 Reservoir Rd. NW, Washington, DC 20007.

REFERENCES

Howard PA, Ellerbeck EF. Optimizing beta-blocker utilization after acute myocardial infarction. Am Fam Physician 2000;62:1853-60,1865-66.

Beta-Blocker Heart Attack Study Group. The beta-blocker heart attack trial. JAMA 1981;246:2073-4.

Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998;339:489-97.

Bero LA, Grilli R, Grimshaw JM, Harvey E, Oxman AD, Thomson MA. Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings. BMJ 1998;317:465-8.

Oxman AD, Thompson MA, Davis DA, Haynes RB. No magic bullets: a systematic review of 102 trials of interventions to improve professional practice. Can Med Assoc J 1995;153:1423-31.

Family Physicians and Accutane

DANIEL J. VAN DURME, M.D.
University of South Florida College of Medicine
Tampa, Florida

See article in this issue.

Do you remember the kid in high school who had the worst acne you had ever seen? The taunting or ostracizing experienced by that kid may have caused more permanent emotional scars than the physical scars that may still be visible today. Until isotretinoin (Accutane) became available in 1982, little treatment could be offered to patients with hyperactive sebaceous glands. Isotretinoin has proved to be extremely effective in these worst-case scenarios, often providing years of relief with a single course of medication. We can even use the word "cure"--not just "control"--to describe what happens when this medication is used.

Despite many significant adverse effects, most patients who use isotretinoin are quite happy with the physical and psychologic benefits of treatment.¹ Isotretinoin is also cost-effective compared with conventional acne management.² Nonetheless, many family physicians still will not prescribe isotretinoin. Is this medication really that bad?

Beyond the significant adverse effects that were well known at the time of its FDA labeling by the U.S. Food and Drug Administration, more serious teratogenic effects became apparent in the mid-1980s.³ These reports led to the Pregnancy Prevention Program for Women on Accutane (PPP) developed by the manufacturer, Roche Laboratories, in 1988. The Roche PPP was designed to be a comprehensive plan for preventing further teratogenic problems associated with the use of isotretinoin and for gathering information for future monitoring. The program provides educational materials for patients and physicians, and a detailed informed consent form. The essential elements of the program are designed to prevent any possibility of pregnancy occurring during a course of therapy with isotretinoin.

While this program has doubtless prevented many problems, about 900 exposed pregnancies were reported over the past 10 years.⁴ Some of the reasons for exposure included failure to use appropriate contraception, failure of the method of contraception and reinitiation of the use of an old prescription. Physicians must share some of the blame for inadequate monitoring of pregnancy tests or insufficient patient education.

While the teratogenic effects of isotretinoin are preventable with appropriate precautions, the other adverse effects are common but manageable. These issues are well reviewed in the article by Johnson and Nunley⁵ in this issue of American Family Physician. The list can seem daunting and will doubtless scare many patients (or the parents of adolescents) away from the medication. Nonetheless, these problems need not stop family physicians from prescribing an effective therapy. Many patients needlessly suffer with nodulocystic acne when their family physician will not prescribe isotretinoin and access to a dermatologist is not possible.

The protocol for prescribing this medicine need not be difficult. A PPP kit may be obtained from Roche Laboratories (telephone: 800-937-6243). Discussion about the drug may be initiated when trying the second or third oral antibiotic, and the "Proper Use of Accutane in Acne" patient education handout that accompanies the article⁵ in this issue can be given to the patient with the explanation that isotretinoin may be needed if the current medicines fail.

For women, the need for contraception can be addressed and may necessitate a separate visit just for contraceptive counseling. At follow-up, questions about the medicine can be answered, initial laboratory tests performed and a prescription given to gradually increase the dosage to 1 mg per kg per day over one month. Follow-up laboratory tests (which may include a pregnancy test) can be performed in three to four weeks and reviewed at the one-month follow-up visit, at which time the prescription for the next month's medication is given. Some clinicians--myself included--will not write prescriptions for refills. This schedule of monthly laboratory tests, visit and then prescription improves the likelihood that side effects are managed promptly and medication is taken appropriately.

Some family physicians feel that the potential for profound adverse effects is not worth the time and effort associated with prescribing isotretinoin. However, the desire for treatment is not just an issue of vanity on the part of our patients. These nodulocystic lesions may be painful, and the potential for physical and emotional scars is very real. By monitoring and quickly managing the adverse effects and helping to avoid teratogenic effects, we can comfortably provide an effective treatment that is well within the scope of practice of most family physicians.

Daniel J. Van Durme is an associate professor of family medicine at the University of South Florida College of Medicine, Tampa.

Address correspondence to Daniel J. Van Durme, M.D., University of South Florida College of Medicine, Department of Family Medicine, 12901 Bruce B. Downs Blvd., Box 13, Tampa, FL 33612-2815.

REFERENCES

Layton AM, Seukeran D, Cunliffe WJ. Scarred for life? Dermatology 1997;195(suppl 1):15-21.

Saurat JH. Systemic retinoids. What's new? Dermatol Clin 1998;16(2):331-40.

Birth defects caused by isotretinoin--New Jersey. MMWR Morb Mortal Wkly Rep 1988;37:171-2, 177.

Accutane-exposed pregnancies--California, 1999. MMWR Morb Mortal Wkly Rep 2000;49:28-31.

Johnson BA, Nunley JR. Use of systemic agents in the treatment of acne vulgaris. Am Fam Physician 2000;62:1823-30,1835-6.

Urinary Tract Infections: 2000 Update

JONATHAN H. ROSS, M.D.
Cleveland Clinic Foundation
Cleveland, Ohio

See article in this issue.

The American Academy of Pediatrics (AAP) Practice Parameter on Urinary Tract Infections that is presented in this issue of American Family Physician¹ is a timely one. Recent studies have brought into question some of the accepted standards in managing these patients, and many of these issues are addressed by the Practice Parameter.

Considering the diagnosis of urinary tract infection (UTI) in a child with an unexplained fever seems obvious, but confirming infection is problematic. Suprapubic aspiration is the recommended means of obtaining a culture specimen^2,3; however, it is unrealistic to expect this practice to be widely accepted. The procedure is anxiety-provoking for the parent and the physician.

Urethral catheterization is a more realistic approach when an accurate diagnosis of UTI is essential, which is the case for most febrile infants. However, the "bag" specimen has its role in the diagnosis of pediatric UTIs. The parameter guidelines¹ seem reasonable in this regard. They suggest that a bag specimen may be obtained in children who do not require immediate therapy. In this setting, if the urinalysis, culture and clinical parameters are taken together, the results can usually be interpreted in a reliable way. However, a bag specimen is not optimal in patients who are given antibiotics; the specimen may be contaminated and, after the administration of antibiotics, the opportunity to get another specimen is gone because the infection will be partially treated.

Urinalysis and culture should always be obtained. A microscopic analysis of the urine to quantify the degree of pyuria is particularly important in distinguishing infection from contamination when the culture is equivocal. Conversely, a negative dipstick urinalysis cannot be relied on to rule out a UTI.

The issue of "asymptomatic bacteriuria" is an important and often misunderstood one. It is well established that asymptomatic bacteriuria is common, difficult to eradicate and of no significance to the patient in the absence of vesicoureteral reflux or other urinary tract anomalies.⁴

The potentially harmful practice of "routine cultures" in asymptomatic patients with a history of UTI is widespread and should be discouraged. These cultures, if positive, will lead to the inappropriate treatment of bacteriuria. This exposes the child to unnecessary antibiotics and select resistant organisms, which will make future symptomatic infections more difficult to treat. Once a child's urinary tract has been shown to be normal by the appropriate radiographic studies, cultures should only be obtained if the child is symptomatic.

By far, the most controversial area in the management of pediatric UTIs is evaluation with imaging studies. Recently, the connection between vesicoureteral reflux and the long-term risks of hypertension and renal failure has been questioned.⁵

This has led some authors to suggest that vesicoureteral reflux is not an important entity and that voiding cystourethrograms (VCUGs) may be unnecessary in children with UTIs.⁵ The argument against the routine use of VCUGs in children with UTIs starts with the premise that many, if not all, of the renal changes seen in children with reflux are actually congenital areas of dysplasia rather than acquired scars resulting from infections. Furthermore, no strong evidence exists linking acquired renal scarring (as opposed to congenital dysplasia) and long-term risk of hypertension and renal failure. Also, evidence is lacking to suggest that medical or surgical management of reflux is any better at preventing long-term complications than simply treating UTIs aggressively when they occur. The argument concludes that VCUGs are unnecessary because there is no proven benefit to aggressive management of reflux.

While this argument raises some important issues, it does not tell the whole story. While some renal abnormalities in children with reflux are undoubtedly congenital, there is evidence that some of these changes are acquired. In 1992, researchers⁶ demonstrated in a prospective fashion that approximately 40 percent of patients with pyelonephritis confirmed by dimercaptosuccinic acid (DMSA) renal scan will develop a new scar in the same location as the area of inflammation on the original scan. Interestingly, although children with vesicoureteral reflux are more likely to get pyelonephritis, once pyelonephritis occurs, the risk of subsequent scarring is independent of the presence or absence of reflux.²

Thus, vesicoureteral reflux promotes renal scarring because it predisposes to pyelonephritis. The long-term significance of these acquired scars is indeed unclear and should be studied. However, to assume that this loss of normal renal tissue is a benign event in the absence of evidence seems unreasonable. Because reflux clearly puts a child at risk for renal injury, the burden is on those who would ignore the entity to prove that it is of no significance. Until such time, it seems reasonable to look for and treat reflux aggressively. Reflux occurs in 30 to 50 percent of children with a UTI.⁷ A renal ultrasound is normal in 75 percent of children with reflux.⁸ Therefore, children with a UTI should undergo a VCUG if reflux is thought to be an important entity.

The AAP Practice Parameter serves as a good start in developing a practical approach to evaluating and managing children from two months to two years of age with a febrile illness. These are children at highest risk for reflux and most likely to suffer renal scarring if pyelonephritis occurs. As children get older, the significance of reflux probably diminishes because new renal scarring appears to be less likely in older children. Furthermore, VCUGs appear to be more upsetting for older children. The obvious question is: "At what age does the morbidity of the VCUGs and subsequent treatment of reflux outweigh the risk of undetected reflux?" A reasonable approach, given current information, would be to obtain a VCUG in any child who has a UTI before toilet training. In older children, VCUG could be reserved for those with febrile or recurrent infections. However, studies on the morbidity associated with VCUGs are needed. The morbidity appears to be related to that of urethral catheterization. Thus, it is interesting that practitioners who would not hesitate to catheterize a child to obtain a reliable urine sample agonize over the issue of whether to obtain a VCUG.

The Practice Parameter of the AAP⁹ offers a sound approach to febrile infections in infants and young children. In the absence of clear-cut data regarding UTIs in children, we should be conservative and do our best to protect children from the possibility of renal injury. Because we know that pyelonephritis can lead to irreversible renal damage, it seems prudent for the time being to treat reflux aggressively. However, we should not hesitate to question established approaches to these problems in an appropriate fashion--with well-designed prospective studies. In this way, we can further refine our management of this relatively common problem.

Jonathan H. Ross is the head of the Section of Pediatric Urology at the Cleveland Clinic Foundation in Cleveland, Ohio.

Address correspondence to Jonathan H. Ross, M.D., Section of Pediatric Urology, Cleveland Clinic Foundation, 9500 Euclid Ave., A100, Cleveland, OH 44195.

REFERENCES

Roberts KB. The AAP Practice Parameter on Urinary Tract Infections in Febrile Infants and Young Children. Am Fam Physician 2000;62:1815-22.

Marks MI, Arrieta AC. Genitourinary tract infections. In: Textbook of pediatric infectious diseases; 4th ed. Feigin RD, Cherry JD, eds. Philadelphia: Saunders, 1998;489.

Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH Jr, Powell KR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Pediatrics 1993;92:1-12.

Jodal U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am 1987;1:713-29.

Ortigas AP, Cunningham AS. Three facts to know before you order a VCUG. Contemp Pediatr 1997;14:69-79.

Rushton HG, Majd M, Jantausch B, Wiedermann BL, Belman AB. Renal scarring following reflux and nonreflux pyelonephritis in children: evaluation with 99m-technetium-dimercaptosuccinic acid scintigraphy. J Urol 1992;147:1327-32.

Smellie J, Edwards D, Hunter N, Normand IC, Prescod N. Vesico-ureteric reflux and renal scarring. Kidney Int Suppl 1975;suppl 4:s65-72.

Blane CE, DiPietro MA, Zerin JM, Sedman AB, Bloom DA. Renal sonography is not a reliable screening examination for vesicoureteral reflux. J Urol 1993;150:752-5.

The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children (ac9830). American Academy of Pediatrics 1999. Retrieved September 2000, on the Web at http://www.aap.org/policy/ac9830.htm.

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