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Treatment of Erythema Multiforme in Children
Erythema multiforme is a self-limiting skin condition characterized by the abrupt appearance of red papules of various sizes, some of which evolve into target lesions. It has been determined that erythema multiforme is often precipitated by herpes simplex virus (HSV) infection. Weston and Morelli conducted a retrospective case series evaluation of 12 children with erythema multiforme to examine its clinical associations, frequency and evolution, and the response to antiviral treatment with acyclovir.
Twelve children (7 boys and 5 girls) in whom HSV-associated erythema multiforme developed were evaluated. Mean age at disease-onset was 8.1 years. Eight of the children had a history of preceding herpes labialis and two children had a history of herpes facialis. Two children had no history of an obvious HSV lesion. The children were seen initially in consultation and were followed for a minimum of three years.
During the initial clinic visit, cultures for HSV were obtained from preceding herpes lesions; biopsies were obtained from early papules, and frozen sections were analyzed for HSV DNA sequences after polymerase chain amplification. HSV was detected in the biopsies of all 12 children, including two children with negative viral cultures and the two children with no history of an HSV lesion. All the children were examined during subsequent attacks of erythema multiforme, and the duration of lesions was determined by follow-up visits. Response to therapy with acyclovir was evaluated by a decrease in the mean duration or number of new episodes, or the absence of any recurrences over a three-year period.
The average time from preceding HSV infection to the onset of skin lesions of erythema multiforme was 3.9 days (range: zero to 11 days). Overall, the time from infection with HSV to outbreak of erythema multiforme varied from episode to episode in all the children. The episodes lasted an average of 10.6 days with a mean occurrence of 2.6 episodes annually.
Most lesions associated with erythema multiforme were on the hands and arms, with fewer on the face and legs. There was always complete resolution of symptoms between episodes, and none of the children developed complications of the disease or progressed to erythema multiforme major (also called Stevens-Johnson syndrome).
Four children were initially treated with topical acyclovir without obvious benefit. Six children were treated with oral acyclovir, 25 mg per kg per day for 10 days, at the onset of one or more episodes of erythema multiforme. No alteration in the frequency or duration of their illness was observed. Three children were treated prophylactically with oral acyclovir at a dosage of 20 mg per kg per day for six months and had no episodes of HSV infection or erythema multiforme during this time. For the six months prior to receiving prophylactic acyclovir treatment, these patients averaged 3.5 episodes. During a three-year period after receiving prophylaxis, only one of the children had a recurrence. This recurrence lasted just three days.
The authors conclude that their findings further support the role of HSV in the development of erythema multiforme. In addition, it would appear that topical acyclovir or the treatment of single episodes of erythema multiforme with oral acyclovir has no effect on the clinical course of the skin condition. Consideration should be given to a six-month course of prophylactic acyclovir for children with frequent recurrences of erythema multiforme.
JEFFREY T. KIRCHNER, D.O.
Weston WL, Morelli JG. Herpes simplex virus-associated erythema multiforme in prepubertal children. Arch Pediatr Adolesc Med October 1997;151:1014-6.
Preventive Occupational Therapy in Elderly Patients
It is projected that more than 17 percent of the American population will be 65 years of age or older by the year 2020, compared with about 13 percent in 1995. If current health trends persist, the longer life spans will include poor general health and a lower quality of life. Clark and colleagues evaluated the effectiveness of a preventive occupational therapy program in maintaining physical health, daily functioning and general well-being in the elderly.
The study participants were at least 60 years old, had the capacity to benefit from occupational therapy and lived independently. Patients were recruited at different times of the year to minimize any seasonal effects on the study and to prevent participant interaction. All participants completed a questionnaire on demographic information, followed by a medical history and a physical examination. Participants were then randomized to one of three groups for the nine-month study: a nontreatment control group, an activity ("social") group and an occupational therapy group. Participants in the occupational therapy and social groups were asked not to discuss their treatment with anyone in the other groups. The occupational therapy group attended both didactic and experiential sessions that focused on the selection of meaningful activities that would result in a healthier, more satisfying lifestyle. Each participant was asked to assess the effect of specific activities on his or her personal life, including exercise, nutrition, joint protection and the use of assistive devices. Participants attended two hours of group therapy and nine hours of individual therapy each week. The social group encouraged interaction among members, such as community outings, craft projects and dances. The control group had no interventions. After the nine-month study period, participants completed another questionnaire on health, life satisfaction, symptoms of depression, and physical and social function.
Of the 361 study subjects, 122 were in the occupational therapy group, 120 in the social group and 119 in the control group. Baseline demographic parameters and health status were similar across all three groups. Participants in the occupational therapy group showed significant improvement in functional status scores, specifically in social performance and life satisfaction. Other areas of improvement in this group included perception of pain, physical functioning, and perception of general health and mental health. The other two groups showed declines in these areas over the duration of the study.
The authors conclude that the adage "keeping busy keeps you healthy" is not necessarily true for seniors. Rather, participants in the occupational therapy group were helped to form a daily routine that was health promoting and meaningful. The results of this study suggested that preventive occupational therapy programs may be a component of "successful aging."
GRACE BROOKE HUFFMAN, M.D.
Clark F, et al. Occupational therapy for independent-living older adults. A randomized controlled trial. JAMA October 22, 1997;278:1321-6.
Inhaled Budesonide and Bone Formation in Children
Anti-inflammatory medicines such as inhaled corticosteroids have been shown to be effective in treating asthma. Nevertheless, many physicians hesitate to prescribe inhaled corticosteroids for children because of possible adverse effects on bone growth and formation. Agertoft and Pedersen evaluated the long-term effects of inhaled budesonide on total-body bone mineral density, total-body bone mineral capacity, total-body bone calcium and body composition in children with asthma.
A total of 268 children participated in the controlled, prospective clinical study. The study group included 157 children who were treated with inhaled budesonide at a mean dosage of 504 µg (range: 189 to 1,322 µg) for an average of three to six years. This group was matched by age, weight, height and sex with a control group of 111 children with asthma. Members of the control group had never received inhaled corticosteroids for more than two weeks per year. Exclusion criteria for participation in the study included use of systemic steroids for more than 14 days, use of topical steroids over more than 25 percent of the body (after two years of age) and use of nasal corticosteroids for more than one month per year. The dosage of inhaled steroid in the study group was chosen for a level that controlled clinical symptoms while maintaining the minimum dosage to relieve symptoms. Dual energy photon absorptiometry (DEXA scan) was used to compare the bone mineral density, bone mineral capacity, bone calcium and body composition of children treated with budesonide and children in the control group.
No statistically significant difference was found between the children receiving budesonide and the control subjects with regard to bone mineral density, bone mineral capacity or bone calcium. No correlation was found between these parameters and duration of treatment or cumulative dosage received by the study group.
The authors conclude that treating children with inhaled budesonide for an average of 4.5 years at a mean daily dosage of 504 µg has no detectable effect on the total bone mineral density, total bone mineral capacity, total bone calcium or body composition of children with asthma. The dosage, however, must be tailored to the severity of disease. They caution that this data should not be extrapolated to include other inhaled corticosteroids or higher dosages of budesonide, which may have long-term adverse effects in children.
TERRENCE J. JOYCE
EDITORIAL BOARD STUDENT REPRESENTATIVEAgertoft L, Pedersen S. Bone mineral density in children with asthma receiving long-term treatment with inhaled budesonide. Am J Respir Crit Care Med January 1998;157:178-83.
Prevention of Angiographic Progression of Atherosclerosis
Studies showing benefit from lipid-modifying therapy in patients with established coronary atherosclerosis have confirmed that reducing low-density-lipoprotein (LDL) cholesterol levels may be associated with reduced total and cardiovascular mortality and nonfatal cardiac events. Gemfibrozil was found to reduce the incidence of cardiovascular events in the Helsinki Heart Study. This beneficial result was associated with a gemfibrozil-induced increment of high-density-lipoprotein cholesterol (HDL) levels. Frick and associates conducted a double-blind, randomized study to determine the effectiveness of treatment with gemfibrozil in patients with coronary atherosclerosis who had low HDL levels.
A total of 395 men 70 years of age or younger were randomized to receive either slow-release gemfibrozil in a dosage of 1,200 mg per day or placebo. All patients had previously undergone successful coronary bypass surgery and had HDL cholesterol levels of 1.1 mmol per L (42.5 mg per dL) or less and LDL cholesterol levels of 4.5 mmol per L (174 mg per dL) or less. Coronary angiography was performed at baseline and after 32 months of therapy. Changes in coronary dimensions were assessed by computer-assisted analysis.
From baseline, patients in the gemfibrozil group experienced a 36 percent reduction in triglyceride levels. Total and LDL cholesterol levels were reduced by 5.5 and 4.5 percent, respectively, and HDL cholesterol levels increased by 21 percent from baseline. In the placebo group, triglyceride levels increased 4.6 percent from baseline, total cholesterol increased 5.1 percent, LDL cholesterol levels increased 5.3 percent and HDL cholesterol levels increased by 7.0 percent. The differences between the active treatment group and the placebo group were highly significant.
Diffuse progression of coronary atherosclerosis measured by arteriograms was significantly milder in the gemfibrozil-treated group than in the placebo group in segments unaffected by grafts and in graft-affected segments. By contrast, there was no difference in the average diameter of the segments of the graft-dependent segments in either group. When all types of native coronary segments (unaffected, graft-affected and graft-dependent) were taken into account, there was significantly less progression of focal coronary atherosclerosis in the gemfibrozil group compared with the placebo group.
Progression of focal coronary atherosclerosis was reduced in patients in the gemfibrozil group although the difference was not statistically significant for the primary segment. Expressed as an average per patient change in percent diameter stenosis, lesion progression was milder in the gemfibrozil group when compared with the placebo group, but the differences were not statistically significant. The appearance of new lesions in primary segments did not show a significant difference between the two groups. There was a marked reduction with active treatment in the number of new lesions in the venous aortocoronary bypass grafts.
The authors conclude that the results of this study demonstrate that therapy with gemfibrozil retards angiographic progression of coronary and vein-graft atherosclerosis in a group of post-coronary bypass men selected on the basis of low HDL cholesterol levels at baseline. The data found here support the conclusions of other large trials that active treatment of dyslipidemias after bypass surgery retards the progression of atherosclerosis both in native coronary arteries and in bypass grafts.
The authors conclude that in patients with low HDL cholesterol but normal or only mildly elevated LDL cholesterol levels, reducing the atherogenic remnants of triglyceride- rich lipoproteins and increasing levels of antiatherogenic HDL cholesterol retards the progression of coronary artery disease.
BARBARA APGAR, M.D., M.S.
Frick M, et al. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Circulation October 1997;96:2137-43.
Toxic Side Effects Associated with Use of Kombucha Tea
Various "health beverages," some of which are additives to tea, are reported to cure cancer, decrease blood pressure, relieve arthritis pain and alleviate constipation. Kombucha tea, also known as Manchurian or Kargasok tea, is made by steeping the Kombucha "mushroom" in tea and sugar. Srinivasan and colleagues review the histories of four patients who consumed this tea.
The four patients illustrated in the report received the original culture "mushrooms" from friends. Kombucha samples that have been tested were found to contain large numbers of bacteria, although the U.S. Food and Drug Administration has found no hygiene violations among commercial producers of the tea.
Two of the four patients consumed the tea for symptom relief of specific problems; the other two cited no particular reason. The first patient, who reported drinking two cups of tea daily for two months, had jaundice of six weeks' duration on presentation. After the jaundice developed, she stopped drinking the tea and decreased her alcohol intake. Within seven weeks, all laboratory values returned to normal limits. The second patient reported nausea, vomiting, headache and xerostomia after drinking one-half glass of tea per day for several months. These symptoms disappeared after she stopped drinking the tea but recurred when she began drinking the tea again. The other two patients experienced a variety of signs and symptoms, including shortness of breath, tachycardia, tachypnea, hypotension and throat tightness. These patients were treated for a presumed allergic reaction.
The authors conclude that drinking 4 oz of Kombucha tea may not cause problems in many persons. However, when consumed in larger amounts or by persons with preexisting health problems, the tea could cause a number of health problems. Therefore, physicians should ask patients about the use of alternative therapies, especially when they present with nonspecific complaints.
GRACE BROOKE HUFFMAN, M.D.
Srinivasan R, et al. Probable gastrointestinal toxicity of Kombucha tea. Is this beverage healthy or harmful? J Gen Intern Med October 1997;12:643-4.
Cost of Interferon-Alfa for Chronic Hepatitis C
More than 8,000 Americans die of hepatitis C virus infection annually, and between 35,000 and 180,000 develop the infection. Given these figures, hepatitis C can be considered a principal cause of liver-related disease for which there is currently no definitive cure. Treatment with interferon-alfa has shown promise, with up to 76 percent of patients with hepatitis C virus infection showing an initial biochemical response after six months of treatment. However, only about 10 percent achieve a sustained response in which all biochemical, histologic and virologic evidence of chronic hepatitis C disappears. When treatment is extended to 12 months, an additional 5 to 7 percent of patients achieve a sustained response. Kim and associates analyzed the cost effectiveness of six- and 12-month courses of interferon-alfa therapy using a computer model that incorporated data about the progression of liver disease and response to interferon-alfa.
A randomized trial was simulated comparing three study groups (no treatment, six months of treatment and 12 months of treatment). Patients in the two treatment groups were given 3 million U of interferon-alfa three times a week. Those who achieved sustained remission were then assumed to follow the mortality pattern of the general population. Those who did not achieve remission followed the clinical course prescribed by a natural history model. Costs analyzed included those associated with treating decompensated cirrhosis, hepatocellular carcinoma and liver transplant, all of which were based on published information. The costs of interferon-alfa were based on wholesale prices plus 20 percent. Outcome measures included the number of deaths from liver disease, the total cost and the effect on the quality of life over time (quality-adjusted life years [QALYs]).
The computer model estimated that the effect of interferon-alfa therapy on hepatitis C was small. The lifetime risk of decompensated cirrhosis decreased from 34.5 percent in patients with no treatment to 31.5 percent in patients with 12 months of treatment. The proportion of patients who died of liver disease decreased from 26.5 to 24.3 percent in the same patients. Analysis of cost effectiveness showed that interferon-alfa therapy ($4,000 per QALY for six months of therapy and $5,000 per QALY for 12 months of therapy) compares favorably with other medical interventions, such as screening mammography ($20,000 per year of life) or cholesterol reduction for secondary cardiac prevention ($45,000 per year of life). However, under certain conditions (such as among older patients, who have poorer results with interferon-alfa therapy), the costs may exceed the amount acceptable to society for other medical interventions. Obviously, if the cost of interferon-alfa were reduced or if treatment were discontinued in patients who did not respond to treatment, cost effectiveness figures would improve markedly.
The authors conclude that although therapy with interferon-alfa is not necessarily ideal in patients with hepatitis C virus, its cost effectiveness after 12 months compares favorably with other widely used medical interventions. Cost effectiveness may improve if drug costs decrease and if treatment failures are identified early. Continuing treatment for 12 months in patients who achieve an initial response after one month, particularly in those with aggressive disease, appears to be appropriate.
In a related article, Bennett and associates also concluded that a six-month course of interferon-alfa in patients with mild chronic hepatitis C is cost effective, particularly in younger patients.
RICHARD SADOVSKY, M.D.
Kim WR, et al. Cost-effectiveness of 6 and 12 months of interferon-a therapy for chronic hepatitis C. Ann Intern Med November 15 1997;127:866-74, and Bennett WG, et al. Estimates of the cost-effectiveness of a single course of interferon-a2b in patients with histologically mild chronic hepatitis C. Ann Intern Med November 15, 1997;127:855-65.
Renoprotective Effect of Enalapril in Diabetic Patients
The long-term effects of poorly controlled diabetes are well known and have a significant adverse impact on the quality of life of those affected. One such adverse effect is diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibitors have been shown to have a renoprotective effect in hypertensive patients with diabetes. Although evidence indicates that diabetic nephropathy cannot be cured, persuasive data exist indicating that its clinical course can be modified by tighter control of blood glucose levels, lifestyle modifications and normalization of blood pressure. Ahmad and colleagues conducted a randomized, single-blind, placebo-controlled study to determine the long-term efficacy of enalapril in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 (noninsulin-dependent) diabetes mellitus.
The study included 103 nonobese, normotensive patients with type 2 diabetes who were followed for five years. Patients were randomly assigned to receive either placebo or 10 mg enalapril daily. Albumin excretion, blood pressure, fasting plasma glucose, HbA1, serum creatinine, and serum and urinary electrolytes in 24-hour urine samples were checked every three to four months. In patients who received enalapril, albumin excretion decreased from a mean of 55 mg per minute at baseline to 20 mg per minute after five years; in the placebo group, albumin excretion increased from a mean of 53 mg per minute at baseline to 85 mg per minute after five years. Within five years, 7.7 percent of enalapril-treated patients and 23.5 percent of placebo-treated patients progressed to clinical albuminuria (defined as albumin excretion rate of greater than 200 mg per minute).
This study corroborates previous evidence of the renoprotective effect of ACE inhibitors in patients with type 2 diabetes and persistent microalbuminuria. The authors conclude that normotensive patients with type 2 diabetes and microalbuminuria experienced a significant reduction in urinary protein excretion that should slow the progression to end-stage renal disease.
JIM NUOVO, M.D.
Ahmad J, et al. Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care October 1997;20:1576-81.
EDITOR'S NOTE: Physicians should screen patients with diabetes for diabetic nephropathy according to the guidelines published by the American Diabetes Association and prescribe ACE inhibitors for normotensive diabetic patients with type 2 diabetes and microalbuminuria.--j.n.
Food Hypersensitivity and Atopic Dermatitis in Children
The role of allergy in atopic dermatitis is unclear. IgE-mediated hypersensitivity may play a part in the pathogenesis of atopic dermatitis, with 50 percent of patients eventually having asthma and 80 percent having asthma or allergic rhinitis. Also, about two thirds of patients have a family history of atopy. Increased IgE concentrations can be found in 80 percent of these children, with most having positive immediate skin test reactions to various dietary and environmental allergens. The identification of food hypersensitivity and elimination of the offending foods from the diet significantly improve atopic dermatitis. Burks and associates examined the prevalence of food hypersensitivity in patients with atopic dermatitis and assessed the use of skin-prick tests with a limited number of food allergens.
A total of 165 patients from four months to 21.9 years of age with mild to severe dermatitis underwent allergy skin-prick tests with a battery of at least 12 food antigens, plus other foods that parents thought were causing symptoms. Parents were then asked to eliminate specific foods from the diet based on the results of the skin-prick test. After two to three weeks, a double-blind, placebo-controlled food challenge was performed with random sequences of placebo and food content. All reactions were recorded.
Ninety-eight patients (60 percent) had at least one positive food skin-prick test. When challenged with the offending food, positive symptoms demonstrated a 100 percent sensitivity, 66 percent specificity, 65 percent positive predictive value and 100 percent negative predictive value for skin testing. The onset of symptoms occurred within two hours of ingesting the food antigen in all cases and consisted mainly of skin symptoms. Other symptoms included gastrointestinal distress and respiratory symptoms. Seven foods (milk, egg, peanut, soy, wheat, cod/catfish and cashew) accounted for 89 percent of the positive challenges. Evaluating the utility of limited skin-prick testing for these seven foods resulted in a positive test having 97 percent sensitivity, 61 percent specificity, 61 percent positive predictive value and 97 percent negative predictive value.
The authors conclude that a large number of patients with atopic dermatitis have positive food challenges. This appears to be exacerbated by IgE-mediated mechanisms. Food elimination diets based solely on history have proved to be inadequate. Children with atopic dermatitis that is unresponsive to routine therapy should be evaluated for food hypersensitivity with a food challenge guided by skin-prick tests. Screening for food hypersensitivity should include milk, egg, peanut, wheat, soy, fish and tree nuts. Since sensitivity decreases or ends in a significant number of children, repeat challenges are a necessary part of ongoing care.
RICHARD SADOVSKY, M.D.
Burks AW, et al. Atopic dermatitis and food hypersensitivity reactions. J Pediatr January 1998;132:132-6.
Adverse Effects in Patients with Polymyalgia Rheumatica
Polymyalgia rheumatica is a disease characterized by pain and stiffness in the proximal regions of the extremities and the trunk. It tends to occur in middle-aged and elderly persons who often experience pain and stiffness for a month or longer before diagnosis. Standard therapy consists of oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or both. Because these medications are associated with adverse side effects, Gabriel and colleagues performed a retrospective study to analyze the long-term incidence and risks of adverse events associated with their use in patients diagnosed with polymyalgia rheumatica.
The authors reviewed an extensive database of patients who were part of the Rochester (Minn.) Epidemiology Project and identified all patients diagnosed with polymyalgia rheumatica between 1970 and 1991. Diagnostic criteria included an age of 50 years or older; a sedimentation rate of 40 mm per hour or more; and bilateral pain and morning stiffness for at least one month involving two of the following areas: neck or torso, shoulders or proximal regions of the arms. When the diagnosis was questionable, three rheumatologists independently reviewed the patient's medical data and reached a consensus. A total of 232 patients were included in the study. Patients were then categorized into three groups: those treated with corticosteroids alone, those treated with NSAIDs alone and those treated with both. Data on adverse events often associated with steroid or NSAID use were collected. These events included diabetes mellitus, symptomatic vertebral fractures, hip fractures, femoral neck fractures, wrist fractures, avascular necrosis, bacteremia or sepsis, upper gastrointestinal bleeding, pneumonitis, cataracts, hypertension and myopathy. Follow-up for all patients continued until death, relocation or January 1, 1992.
The mean age at diagnosis of polymyalgia rheumatica was 72.9 years, and the average follow-up time was eight years. Among the 175 patients treated with corticosteroids (with and without NSAIDs), the mean duration of therapy was 2.4 years, and the average daily dosage was 9.6 mg. A total of 282 adverse events were recorded after polymyalgia rheumatica was diagnosed in 160 of the 232 patients. Patients who received corticosteroid therapy with NSAIDs were more likely to experience adverse events. Sixty-seven percent of patients treated only with NSAIDs and 65 percent of patients treated with only a corticosteroid had at least one adverse event. The average time from initiation of therapy to the first adverse event was 1.6 years for all patients who had adverse events. The most common events included cataracts, infections, hypertension and vertebral fractures. The risks of diabetes, vertebral fracture, femoral neck fracture and hip fracture were two to five times greater in patients with polymyalgia rheumatica than in age- and sex-matched control subjects from the same population. Patients who did not receive medical care or consultation from a rheumatologist received an average initial daily dosage of prednisone that was 9.5 mg higher than the dosage in patients who did have a rheumatologist involved in their medical care. The three variables found to independently increase the risk of an adverse event were female sex, older age at diagnosis and a cumulative dose of prednisone in excess of 1,800 mg.
The authors conclude that although the duration of treatment for polymyalgia rheumatica is often short and the dosages of corticosteroids and NSAIDs used to treat this condition are low, there is a high incidence of adverse events, and they are associated with significant morbidity. Physicians should be vigilant about maintaining patients with polymyalgia rheumatica on the lowest dosage of medication for the shortest period of time that is clinically necessary.
JEFFREY T. KIRCHNER, D.O.
Gabriel SE, et al. Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica. Arthritis Rheum October 1997;40:1873-8.
EDITOR'S NOTE: Although this is a retrospective study, its results still point out the risks of treating elderly patients with long-term corticosteroids. The decision to initiate corticosteroid therapy may be especially difficult in a patient with a condition such as polymyalgia rheumatica--a disease that must be diagnosed clinically and whose etiology remains unknown. A rapid response to corticosteroid therapy is usually the rule in patients with polymyalgia rheumatica, and this can aid the clinician in confirming the diagnosis. Consultation with a rheumatologist is quite reasonable if the diagnosis is uncertain. These patients must then be carefully monitored for the occurrence of the adverse events noted in the study. Preventive measures, which include the addition of calcium, estrogen or bisphosphonate therapy, should be considered in all of these patients.--j.t.k.
Accuracy of Fine-Needle Aspiration Breast Biopsy
Approximately 500,000 open excisional breast biopsies are performed annually in the United States and, of these, more than 80 percent are found to be benign. Various methods to establish an accurate, efficient and less invasive diagnostic technique have been evaluated including mammography, ultrasonography, core needle biopsy and fine-needle aspiration. The latter technique has become increasingly popular in the diagnostic work-up of a palpable breast mass because it can be performed in the physician's office without anesthesia. It is a sensitive, expedient and economical method of obtaining cytologic material for pathologic examination. O'Neil and colleagues performed a retrospective study to evaluate the accuracy of fine-needle aspiration by comparing the cytologic findings with that of histopathology.
Results of Fine-Needle Aspiration of Breast Lesions* Results
Number of samples
Inadequate sample
True positives
True negatives
False positives
False negatives
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Accuracy5 (0.7†)
485 (69†)
153 (24†)
44 (6.0†)
13 (1.9†)
97%
78%
92%
92%
92%
*--Suspicious readings are included as positive readings.
†--Percentage of total.
Adapted with permission from O'Neil S, Castelli M, Gattuso P, Kluskens L, Madsen K, Aranha G. Fine-needle aspiration of 697 palpable breast lesions with histopathologic correlation. Surgery October 1997; 122:826.
A retrospective review was performed of the medical records of women who had undergone fine-needle aspiration of a palpable breast lesion followed by a histopathologic confirmation of the diagnosis. The procedure for histopathologic confirmation of the diagnosis included an open excisional biopsy, a core-needle biopsy or a mastectomy specimen. Fine-needle aspiration was performed using a 23-gauge needle and a 10-mL syringe attached to an aspiration gun. Two separate passes were made into the breast lesion with the needle. The biopsy specimens were then fixed in alcohol and stained with Papanicolaou stain. On examination, they were assigned one of three diagnoses: malignant, suspicious or benign.
A total of 697 cases fulfilled study criteria. A diagnosis of "malignant" was made for 401 (58 percent) of these specimens. The positive predictive value of a malignant reading was 99 percent. A diagnosis of "suspicious" was made for 125 specimens (18 percent). Of these, 84 (67 percent) were malignant and 41 (33 percent) were benign or "false suspicious." A total of 166 of the 697 specimens were read as "benign" (24 percent) and, of these, 153 were true-negative benign lesions (92 percent). A small number of these (5 percent) were fibroadenomas; the rest were fibrocystic disease. Thirteen lesions diagnosed as benign were found to be malignant on histopathologic examination. This represented a false-negative rate of 1.9 percent for the entire series. The false-negative specimens tended to be the types of lower-grade and slower-growing tumors that have a better prognosis. These results were thought to be sampling problems and not interpretation errors.
The authors conclude that fine-needle aspiration is a highly sensitive method for evaluating palpable breast masses for malignancy. When a definitive tissue diagnosis can be made, it is highly predictive of the mass being positive or negative for cancer. However, fine-needle aspiration should never be the sole diagnostic modality used to determine treatment interventions.
JEFFREY T. KIRCHNER, D.O.
O'Neil S, et al. Fine-needle aspiration of 697 palpable breast lesions with histopathologic correlation. Surgery October 1997;122:824-8.
Nebulizers vs. MDIs with Spacers for COPD or Asthma
Nebulizer treatment is recommended for the management of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) or asthma who visit the emergency department for urgent care. However, nebulizer treatment requires special equipment and regular maintenance, uses up to 10 times more medication than metered-dose inhalers (MDIs) and is a potential source of contamination. Mandelberg and associates compared nebulizer treatment with therapy administered with an MDI and a spacer.
The study group consisted of 50 patients who presented to an emergency department for treatment of a severe respiratory event. Each patient was randomized to one of two groups. The first group received an MDI and a spacer with placebo followed by a nebulized treatment with medication. The second group received an MDI and spacer with medication and a nebulized treatment with placebo. The assigned treatment was repeated every 15 minutes up to three times unless the patient suffered significant side effects. Spirometry was performed initially and after each treatment. The patients and an investigator rated symptom response after the treatments.
The results of spirometry did not differ between the two groups. Subjective improvement, as rated by the patients and the investigators, did not differ.
The authors conclude that even in patients who present to the emergency department for treatment of severe airflow limitations, treatment with an MDI and a spacer is appropriate. This therapy can be as effective as nebulizer therapy, and it may reduce the cost of treatment in these patients. The use of an MDI with a spacer requires less equipment, reduces the demand on personnel time and can reduce the risk of contamination.
KARL MILLER, M.D.
Mandelberg A, et al. Nebulized wet aerosol treatment in emergency department--is it essential? Chest December 1997;112:1501-5.
Minimally Invasive Incision vs. Sternotomy for Valve Repair
Median sternotomy, cardiopulmonary bypass and various degrees of systemic hypothermia are used in classic surgery to repair or replace cardiac valves. Minimally invasive, or "key hole," surgery has recently been used to minimize surgical trauma and shorten the hospital stay and rehabilitation period. Cohn and associates compared the quality of valve replacement and repair through a minimally invasive incision with that of standard median sternotomy.
Patients with concomitant major coronary artery disease were excluded from the analysis. Forty-one patients who underwent aortic valve surgery and 43 patients who underwent mitral valve surgery through minimally invasive incisions were studied prospectively. In addition, the authors compared cost, length of hospital stay and need for rehabilitation services after hospital discharge in the first 50 patients who had undergone minimal procedures with those same parameters in 50 patients who had undergone standard valve replacement through a median sternotomy.
The surgical mortality was 5 percent (two of 41 patients) for aortic valve surgery and zero for mitral valve surgery. The two deaths occurred in class IV patients (one death was associated with liver failure and one with arrhythmia). No infections of the thoracic incision developed. One patient required conversion to sternotomy after aortic valve replacement because of a coronary sinus injury related to use of a catheter. There was one postoperative death. Other significant morbidity included one transient ischemic attack and one cerebrovascular accident.
Patients improved by at least two functional classes in the New York Heart Association classification. Less pain, less pain medication and a significantly faster return to normal activity were documented in the patients who had minimally invasive incisions, compared with patients who had undergone similar procedures with median sternotomy.
The authors note that a disadvantage of the minimally invasive approach is the need to use the femoral area for cannulation and perfusion in many patients. The authors note that retrograde dissection may occur. Thus, the thoracic aorta is monitored for severe atherosclerotic changes before using the technique. The rate of groin complications was 8 percent (seven of 84 patients); three had superficial infections, and four required intraoperative arterial reconstruction.
The authors conclude that the quality of cardiac valve surgery with a minimally invasive incision appears to be equal to that of the sternotomy approach. A minimally invasive incision, however, may not be as useful in extremely ill patients with a high degree of risk and potential morbidity. The minimally invasive approach requires longer ischemia and bypass times.
RICHARD SADOVSKY, M.D.
Cohn LH, et al. Minimally invasive cardiac valve surgery improves patient satisfaction while reducing costs of cardiac valve replacement and repair. Ann Surg October 1997;226:421-8.
Conservative Management of Ovarian Dermoid Cysts
Dermoidal cysts commonly develop during the reproductive years. The traditional treatment for these cysts has been surgical intervention; however, this treatment can impair fertility. Caspi and associates designed a study that used ultrasound scanning as a way to follow patients with dermoid cysts that were 6 cm or smaller.
The diagnosis of dermoid cyst was determined by the presence of one of three unique pathognomonic features. The study observed 86 women who had an ovarian dermoid cyst no larger than 6 cm who were followed with ultrasound examination at three and nine months, and then annually.
The results of the study indicated that the average annual growth rate of ovarian dermoid cysts for premenopausal women was 1.77 cm. In postmenopausal women the average annual growth rate was -1.59 cm. When compared to zero, the premenopausal growth rate was significant; the postmenopausal growth rate was not. Of the patients who entered the study, 24 (28 percent) had surgery to remove the cyst, 21 of whom underwent surgery because the growth rate was over 2 cm per year. During the study, 28 women (32 percent) conceived while a cyst was present. There was no cyst torsion or malignant transformation in any of the patients during the follow-up period.
The authors conclude that dermoid cysts no larger than 6 cm can be managed conservatively with ultrasound scanning, provided the annual growth rate does not exceed 2 cm. The growth rate of these cysts tends to be slow, and complication rates are low. This management strategy allows women who are planning families an opportunity to observe dermoid cysts and postpone surgical intervention that could impair fertility. These cysts can also be observed in postmenopausal women, because the growth rate is slow and the cyst may actually decrease in size.
KARL MILLER, M.D.
Caspi B, et al. The growth pattern of ovarian dermoid cysts: a prospective study in premenopausal and postmenopausal women. Fertil Steril September 1997; 68:501-5.
Buproprion Therapy as an Aid for Smoking Cessation
Pharmacologic treatment such as nicotine replacement therapy has been shown to help some people stop smoking. The idea of using a non-nicotine product such as an antidepressant as an aid for smoking cessation has been intriguing, since people who smoke are more likely to have a history of depression than nonsmokers. However, results of clinical trials of antidepressant therapy as aids for smoking cessation, such as those involving doxepin and selective serotonin reuptake inhibitors, have been mixed. Hurt and associates conducted a randomized, double-blind, placebo-controlled study to evaluate the effectiveness of a sustained-release form of bupropion as an aid to smoking cessation.
Patients were recruited for the study through advertisements and press releases. To be eligible, patients had to be at least 18 years of age, to have smoked at least 15 cigarettes per day for the past year, to be motivated to quit smoking and to be in generally good physical health. Exclusion criteria included a personal or family history of seizures, current use of psychotropic medications, current use of any nicotine-replacement products, a history of alcohol dependence, and pregnancy. Patients who currently had depression as determined by the physician were excluded; however, those with a history of stable major depression were allowed to participate.
At baseline, patients were randomized to one of four treatment groups and were then given a sustained-release form of bupropion at dosages of either 100 mg, 150 mg or 300 mg per day, or placebo. The patients were followed weekly during the seven weeks of the treatment phase. They were then evaluated at eight, 12, 26 and 52 weeks for further follow-up.
A total of 615 patients were included in the study, but 219 did not complete the 12-month study period. By the end of the seven-week treatment phase, 19 percent of patients in the placebo group had stopped smoking, compared with 28.8 percent of patients receiving 100 mg of bupropion, 38.6 percent of patients receiving 150 mg of bupropion and 44.2 percent of patients receiving 300 mg of bupropion daily. At one year, the rate of smoking cessation was 12.4 percent in the placebo group, 19.6 percent in the group receiving 100 mg, 22.9 percent in the group receiving 150 mg and 23.1 percent in the group receiving 300 mg. Results in the groups receiving 150 and 300 mg were significantly different from those in the groups receiving placebo or 100 mg per day of buproprion.
The study also evaluated weight gain in all participants and found that the mean weight gain was inversely associated with the dosage of bupropion. Patients receiving 300 mg of bupropion daily had an average weight gain of 1.5 kg at one year compared with 2.9 kg in the placebo group. Adverse events associated with bupropion resulted in treatment cessation by 29 patients. The most common adverse reactions included tremor, headaches, rash and urticaria. Other adverse effects included insomnia and dry mouth.
The authors conclude that sustained-release bupropion is an effective aid for smoking cessation with minimal side effects. Dosages of 150 and 300 mg of bupropion per day are more effective than a 100-mg dosage. An additional advantage appears to be a diminished weight gain, avoiding what is often a deterrent for people who attempt to quit smoking.
JEFFREY T. KIRCHNER, D.O.
Hurt RD, et al. A comparison of sustained-released bupropion and placebo for smoking cessation. N Engl J Med October 23, 1997;337:1195-202.
Delivery of the Placenta by Means of Active Intervention
The most common causes of postpartum hemorrhage are uterine relaxation and atony. In the United States, delivery of the placenta is usually followed by intravenous administration of oxytocin to contract the uterus and prevent further bleeding. In Canada, however, active management of the third stage of labor is more commonly practiced, and oxytocin is administered before the placenta is delivered. Khan and associates compared the occurrence of postpartum hemorrhage with controlled cord traction and the occurrence with minimal intervention for delivery of the placenta.
A total of 1,648 women were randomly assigned during labor to receive controlled cord traction (827 patients) or minimal intervention (821 patients) for delivery of the placenta. Patients in the controlled cord traction group received oxytocin, 10 U intramuscularly, at the time of delivery of the anterior shoulder, after which the placenta was delivered by controlled cord traction. In the minimal intervention group, the placenta was delivered by maternal pushing, and no traction was applied to the cord. Continuous intravenous oxytocin was administered after placental delivery.
The incidence of overall postpartum hemorrhage (defined as more than 500 mL) or hemorrhage of more than 1,000 mL was significantly lower in the controlled cord traction group. The median blood loss was 200 mL in the controlled cord traction group, compared with 250 mL in the minimal intervention group. The incidence of placenta retained for longer than 30 minutes was significantly lower in the controlled traction group. Twelve patients (1.5 percent) in this group had retained placenta, compared with 37 patients (4.5 percent) in the minimal intervention group. Four patients in the minimal intervention group and one patient in the controlled cord traction group required blood transfusion. Significantly more patients in the minimal intervention group (42 patients versus 19 patients) required ergot or prostaglandin to control blood loss.
The authors conclude that the controlled cord traction technique for third-stage management is associated with a significantly lower incidence of postpartum hemorrhage compared with minimal intervention. They note some concern that the administration of intramuscular oxytocin before delivery of an undiagnosed twin gestation would compromise delivery of the second twin. In this study, prenatal ultrasonographic examination was performed in all of the patients. When ultrasound assessment is not routinely performed prenatally, administration of oxytocin before delivery of the placenta and controlled cord traction would be a concern. The authors agree with previous studies showing that active management of the third stage of labor by means of controlled cord traction is highly effective in preventing postpartum hemorrhage.
BARBARA APGAR, M.D., M.S.
Khan GQ, et al. Controlled cord traction versus minimal intervention techniques in delivery of the placenta: a randomized controlled trial. Am J Obstet Gynecol October 1997;177:770-4.
EDITOR'S NOTE: The Cochrane review of the childbirth literature reaffirmed the value of active management of the third stage of labor to reduce or prevent postpartum hemorrhage. The studies examined by the Cochrane reviewers showed good consistency and randomization, and demonstrated the effectiveness of this method in reducing postpartum hemorrhage.--b.a.
Routine Replacement of Peripheral IV Catheters
Patients with intravenous catheters may experience phlebitis, catheter-related infections and obstruction of the catheter. In 1981, the Centers for Disease Control and Prevention (CDC) recommended routine replacement of peripheral intravenous catheters every 48 to 72 hours "because of a sharp increase in the rate of infection after this length of time." Guidelines from the CDC in 1996 continued to recommend rotating catheter sites at 48- to 72-hour intervals. Bregenzer and colleagues evaluated the risks associated with leaving peripheral intravenous catheters in place for as long as they are needed.
A total of 451 patients were enrolled in the study, and 609 catheters that were left in place for one to 28 days were evaluated. The study population included consecutive patients in surgical and medical intensive care units. No disinfection was allowed before removal of the catheter to prevent false-negative results. On removal, the catheter was sent for laboratory analysis.
Clinical complications occurred with 156 catheters (25.6 percent). These complications included phlebitis (19.7 percent), catheter-related infections (6.9 percent) and obstructions (6.0 percent). No significant increase was apparent in the day-specific risk for any of the outcome variables after the second day of catheter placement. The mean duration of catheterization was 3.9 to 4.6 days for catheters with obstruction, phlebitis and positive culture results, which did not differ significantly from those without complications. A total of 223 catheters were left in place for more than three days. No catheter-related bloodstream infections occurred in the study subjects.
The authors conclude that a correlation between phlebitis and catheter infection could not be confirmed. The data suggest that the risk depends on the total number of days that a catheter is in place and not on the duration of use of a single catheter. The additional cost and discomfort for the patient do not support routine replacement.
BARBARA APGAR, M.D., M.S.
Bregenzer T, et al. Is routine replacement of peripheral intravenous catheters necessary? Arch Intern Med January 26, 1998;158:151-6.
Tobacco Smoke Exposure and Meningococcal Disease Risk
Neisseria meningitidis is an important cause of bacterial sepsis and meningitis in children, with one third of cases occurring in children under two years of age. An important strategy for preventing meningococcal disease is the identification of modifiable risk factors. Fischer and associates attempted to identify risk factors associated with meningococcal disease.
The study included 129 patients infected with N. meningitidis and 274 age-matched control subjects. Patients or their guardians were interviewed about numerous environmental and activity factors. Questions in the interview referred to the month preceding the patient's illness.
Having a mother who smokes was the strongest independent risk factor for invasive meningococcal infection in children under 18 years of age. A dose-response effect was found between the number of packs the mother smoked per day and the child's risk for disease. After adjusting for all other significant exposures identified, 37 percent of all meningococcal infections in children could be attributed to maternal smoking. An increased number of smokers in the home also had a significant linear relationship with the risk of meningococcal disease.
Other factors found to be independently associated with a risk of meningococcal disease in children under age 18 included having a mother who did not graduate from high school, lacking a primary care physician and living in a household below the poverty level. These factors were not associated with a risk of meningococcal disease in adults. Among adults, the strongest independent risk factor for meningococcal disease was an underlying chronic illness.
The mechanism by which tobacco smoke increases the risk of meningococcal disease is not known. Mechanical effects on respiratory mucosa or functional effects on the immune system may be important.
The authors conclude that exposure to tobacco smoke is an independent risk factor for meningococcal disease in children. The demonstration of a dose-response relationship and the plausibility and reproducibility of these findings strengthen this association. Reductions in smoking, especially among mothers of young children, may decrease the incidence of meningococcal disease.
RICHARD SADOVSKY, M.D.
Fischer M, et al. Tobacco smoke as a risk factor for meningococcal disease. Pediatr Infect Dis J October 1997;16:979-83.
Quality of Life and Early Screening for Osteoporosis
Programs designed to screen perimenopausal women for low bone density are controversial. After screening, women are often given hormone replacement therapy and may be labeled at "high risk" for osteoporosis, which may have a negative impact on their quality of life. From a cost perspective, the most significant expense of a screening program is the hormone replacement therapy, not the cost of measuring bone mineral density (BMD). Torgerson and colleagues evaluated the effect of a screening program on the use of hormone replacement therapy and quality of life.
A total of 1,600 women were selected from a community health index and randomized to either a BMD screening group or a control group. All of the women were 45 to 54 years of age. Women in the screening group were tested and advised of their BMD status, and received lifestyle advice from their physicians. Women in the control group were not screened or contacted at baseline. Baseline characteristics, including height, weight, educational level and history of hysterectomy, were similar in both groups. Two years later, the same women were surveyed to determine use of hormone replacement therapy and quality of life issues. A total of 607 women (76 percent) in the control group and 613 (77 percent) in the screening group completed this survey questionnaire.
Current use of hormone replacement therapy was significantly higher in the screening group than in the control group. A greater proportion of the women receiving hormone therapy cited low BMD or prevention of osteoporosis as the reason for therapy. Women with the lowest BMD in the screening group had a 19 percent increase in the use of hormone replacement therapy compared with women in the control group. In fact, these women were approximately 2.5 times more likely than women in the control group to receive hormone replacement therapy.
The use of therapy also tended to increase with age. The incidence of hormone replacement therapy use did not differ between groups in women 47 to 51 years of age; however, in women 52 to 56 years of age, there was a significant increase in therapy use (13 percent). Quality of life scores and self-reported fall and fracture rates did not differ between groups.
The authors conclude that BMD screening results in a modest increase in the use of hormone replacement therapy and that this increase becomes more evident as women age. However, after two years, screening did not appear to have any effect on quality-of-life issues, although this may change with a longer-term study. The study showed no fracture-related benefits of screening, but such benefits may not be apparent within two years of initial BMD measurements.
BARBARA APGAR, M.D., M.S.
Torgerson DJ, et al. Randomized trial of osteoporosis screening. Use of hormone replacement therapy and quality-of-life results. Arch Intern Med October 13, 1997;157:2121-5.
Oropharyngeal Candidiasis and Candidal Diaper Dermatitis
Oropharyngeal candidiasis (also called oral thrush) and candidal diaper dermatitis are annoying problems that resolve spontaneously in most healthy infants. In some cases, however, the symptoms may be persistent, causing pain, anorexia and discomfort. For these reasons, rapid control is often desirable. Hoppe reviews the management of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants.
Oropharyngeal candidiasis is rare in the first week of life. The peak prevalence of this disorder occurs at four weeks of age. Nonabsorbed agents should be used to treat neonates and infants without major underlying considerations. Gentian violet is moderately effective but may cause irritation and ulceration of the mucosa with prolonged use. Topical nystatin is virtually free of harmful reactions, although high doses of the oral preparation can cause nausea and vomiting. Nystatin suspension has suboptimal efficacy, because its antifungal activity is only moderate. Amphotericin B suspension appears to have slightly better efficacy than nystatin. Neither gentian violet, nystatin nor amphotericin has a clinical cure rate of greater than 80 percent. Miconazole gel and topical clotrimazole appear to be more effective, but miconazole oral gel is not available in the United States, and oral clotrimazole can raise liver enzyme levels and cause gastrointestinal side effects in infants. This lack of an efficacious treatment preparation has led to the unconventional oral administration of topical or vaginal antifungal agents. When miconazole is used, it is probably not necessary to administer the medication beyond the day of clinical cure.
Candidal diaper rash starts in the perianal area and spreads to adjacent areas. Treatment includes aerating the diaper area and keeping the infant dry. Zinc oxide paste may be soothing and protective when the acute phase of the eruption has subsided. Baby powder application also may be useful. Antifungal therapy is mandatory to achieve resolution. Nystatin, amphotericin, miconazole and clotrimazole are all useful, although cure rates are higher with use of miconazole and clotrimazole. Oral treatment of candidal diaper dermatitis and the possible accompanying intestinal infection is recommended by many experts.
The author concludes that for treatment of oropharyngeal candidiasis, miconazole oral gel is clearly superior to nystatin suspension. If nystatin suspension must be used, dosages higher than those conventionally administered might improve the outcome. For topical therapy of candidal diaper dermatitis, several agents appear to be equivalent. The addition of an oral agent to the topical treatment is probably appropriate. Nystatin suspension may be used for this purpose.
RICHARD SADOVSKY, M.D.
Hoppe JE. Treatment of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants: review and reappraisal. Pediatr Infect Dis J September 1997;16: 885-94.
H. pylori Infection and Risk of NSAIDInduced Ulcers
Although Helicobacter pylori is present in about one half of patients with peptic ulceration who use nonsteroidal anti-inflammatory drugs (NSAIDs), it is not known whether H. pylori infection increases the risk of peptic ulceration during NSAID therapy. Chan and colleagues evaluated whether H. pylori infection predisposes patients to NSAIDassociated peptic ulceration and if eradication of the organism before initiation of NSAID therapy would protect patients from this complication.
Ninety-two patients with musculoskeletal disorders that required NSAID therapy participated in the eight-week study. All of the study subjects had H. pylori infection, but none had preexisting ulcers. None of the patients had previous exposure to NSAID therapy. Patients were randomly assigned to begin NSAID therapy immediately or to receive a one-week course of therapy to eradicate H. pylori before starting NSAID therapy. NSAID therapy consisted of 750 mg of naproxen daily in three divided doses. The H. pylori eradication regimen included bismuth subcitrate, tetracycline and metronidazole. Patients were monitored clinically and by repeat endoscopy after eight weeks of naproxen therapy. Pill counts were used to monitor compliance.
The two groups of patients were matched in terms of age, sex, severity of arthritis, smoking and drinking habits. Of the 45 patients who received H. pylori eradication therapy, 40 (89 percent) initially became free of infection. H. pylori persisted in all of the patients who did not receive eradication therapy. Twelve of the patients who did not receive eradication therapy developed peptic ulceration within eight weeks. Five of these patients had pain, and one had gastrointestinal bleeding. Peptic ulcers developed in three of the patients given eradication therapy. Two of these patients subsequently had failure of eradication. Thus, peptic ulcers developed in only one of the patients in whom H. pylori was eradicated before the start of NSAID therapy.
The authors conclude that eradication of H. pylori before the initiation of NSAID therapy reduced the eight-week cumulative rate of NSAID-induced ulcers by almost fourfold. They recommend serologic testing for H. pylori and eradication of the organism before NSAID therapy is initiated.
ANNE D. WALLING, M.D.
Chan FK, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet October 4, 1997;350:975-9.
Oral and Rectal Mesalamine for Ulcerative Colitis
Anti-inflammatory agents such as sulfasalazine, corticosteroids and mesalamine are the primary therapy for ulcerative colitis; the latter is available in both oral and rectal formulations. Safdi and associates studied the effectiveness of oral, rectal or combination mesalamine therapy in patients with ulcerative colitis.
Sixty patients with mild or moderate distal ulcerative colitis were enrolled in the six-week double-blind study. Eighteen patients received mesalamine rectal enemas (4 g once nightly), 22 patients received oral mesalamine (two 400-mg tablets three times a day), and 20 patients received both rectal and oral therapy. Patients who received only oral or rectal therapy were given placebo enemas or capsules to provide each patient with the same treatment regimen.
A disease activity index was completed at baseline and during the third and sixth weeks of the study. Patients also kept a daily diary of the amount of blood in the stool, urgency, straining at stool and abdominal pain. Patients and physicians assessed improvement at the two follow-up visits. Sigmoidoscopy was performed at baseline and at the end of the study.
After six weeks of therapy, the disease activity index showed more improvement in the combination therapy group than in the other two groups. Patients in the combination therapy group reported the absence of bloody diarrhea sooner. The mean number of days until cessation of rectal bleeding was 11.9 in the combination therapy group, 24.8 days in the rectal mesalamine group and 25.5 days in the oral mesalamine group. Rectal bleeding stopped in 89 percent of the combination therapy group, 69 percent of the rectal mesalamine group and 46 percent of the oral mesalamine group. By week 6, physicians rated 85 percent of the combination therapy group "much improved" or "very much improved." This degree of improvement occurred in 45 percent of the oral mesalamine group.
The authors conclude that the combinaton of oral and rectal mesalamine produced earlier and more complete relief of rectal bleeding than either therapy alone. The combination was well tolerated when taken for six weeks. They note that maintenance therapy with mesalamine enema or oral tablets alone would be a cost savings if remission could be sustained with monotherapy.
KARL MILLER, M.D.
Safdi M, et al. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. Am J Gastroenterol October 1997;92:1867-74.
Treatment of Depression in Hospitalized Elderly Patients
Given the strong relationship between physical illness and depression in older adults, medical hospitalization provides an opportunity to diagnose and treat elderly patients with depression. Nearly 40 percent of medically ill elderly patients who are hospitalized experience some form of depression, although only a small proportion of these patients are recognized as being depressed and only about 50 percent of those with major depression receive treatment. The majority of these depressions do not resolve on their own and may persist for many months after hospital discharge. Koenig and associates examined antidepressant and benzodiazepine use as prescribed by nonpsychiatrists before, during and after acute hospitalization in older patients with depression.
A total of 153 hospitalized patients 60 years of age or older were identified by an intensive psychiatric interview and included in the study. Following discharge, the patients were contacted by telephone four times at 12-week intervals to inquire about medication use. Overall, 40.5 percent of the patients received antidepressants at some time during hospitalization or during follow-up after discharge, 25.5 percent of patients received benzodiazepines and 34 percent of patients received neither. During hospitalization, 39.9 percent of patients received benzodiazepines, and 54.1 percent of these patients received new prescriptions. Of the 114 patients with depression who were not receiving antidepressants on admission, only 15 (13.2 percent) started antidepressant therapy while in the hospital.
Of the 62 patients treated with antidepressants, 45.2 percent (28 patients) received amitriptyline and 14.5 percent (nine patients) were treated with other tricyclics, a tetracyclic or a monoamine oxidase inhibitor. Thus, newer and older antidepressants were used with equal frequency. Amitriptyline was prescribed at an average dosage of 48.6 mg per day (a dosage likely to be subtherapeutic even in frail elderly patients). Fluoxetine was prescribed at an average dosage of 28.2 mg per day (a dosage considered to be excessive in many frail elderly patients). Of the 91 patients with depression who were not prescribed antidepressant therapy before or during hospitalization, only 11.0 percent (10 patients) received antidepressant therapy at some time during the one-year follow-up period. In those patients who received antidepressant therapy at discharge, there was little indication that these dosages were titrated up according to patient response.
Comparing the results of this study with results of a study conducted in 1987, the current study did not show that elderly patients with depression were more likely to receive antidepressants. The current study found that these patients received benzodiazepines almost twice as often as patients in 1987. This finding was disturbing because of the association between benzodiazepine use and an increased risk of falls and hip fractures. Amitriptyline was the most commonly prescribed antidepressant in the current study, although it has been associated with strong anticholinergic, antihistaminic and beta-adrenergic blocking properties as well as adverse cardiac conduction events. According to two recent studies, treatment with amitriptyline is considered inappropriate for elderly patients.
The authors conclude that greater attention should be paid to the identification and appropriate treatment of elderly patients with depression. This study evaluated the prescribing habits of nonpsychiatrists in a large teaching hospital. Further educational interventions are needed to ensure that elderly patients receive proper therapy for depression.
BARBARA APGAR, M.D., M.S.
Koenig HG, et al. Use of antidepressants by nonpsychiatrists in the treatment of medically ill hospitalized depressed elderly patients. Am J Psychiatry October 1997;154:1369-75.
Conventional vs. Ambulatory Blood Pressure Measurement
When compared with ambulatory blood pressure measurements, conventional blood pressure measurements are not as highly reproducible, are associated with the so-called "white-coat effect" and must be repeated over a time interval (usually several weeks) in order to provide an idea of the patient's blood pressure range. Staessen and colleagues report on the Ambulatory Blood Pressure Monitoring and Treatment of Hypertension randomized trial that compared conventional and ambulatory blood pressure measurements in the management of hypertensive patients to determine the number and amount of antihypertensive drugs necessary for maintaining blood pressure control.
Patients were recruited from 47 family practices and nine internal medicine clinics. Patients already diagnosed as hypertensive were weaned from their blood pressure medications and began taking placebo once a day. Follow-up visits occurred at one and two months, and patients were then randomized if the last of three conventional diastolic blood pressure measurement readings taken at the follow-up visits averaged from 95 to 114 mm Hg. Once randomized, all patients began taking 10 mg of lisinopril daily. Patients were then seen at one, two, four and six months after randomization. Conventional blood pressure measurements, taken after the patient had been sitting for five minutes, were averaged over three consecutive readings. Signs, symptoms and blood pressure readings (both conventional and ambulatory) were then transmitted to an office where one physician made changes to the medication in a single-blind fashion. If the diastolic blood pressure was above the target range (i.e., higher than 89 mm Hg), the regimen was advanced one step. If the diastolic blood pressure was at the target range of 80 to 89 mm Hg, no change was made, and if diastolic blood pressure was below the target range (less than 80 mm Hg), the regimen was reduced one step. The steps were as follows: begin treatment with 10 mg of lisinopril daily (step 1); increase lisinopril to 20 mg daily (step 2); add 12.5 mg of hydrochlorothiazide daily (step 3); and add 5 mg of amlodipine daily (step 4).
A total of 544 patients enrolled in the study, and 419 were available for analysis. More patients who were managed using ambulatory blood pressure readings were able to discontinue their blood pressure medications, since their diastolic blood pressures stabilized at or below the target range. Of the 56 patients on ambulatory monitoring in whom drug treatment was stopped, more than one half (58.9 percent) had daytime diastolic blood pressure readings of less than 85 mm Hg. Symptom scores decreased similarly in both groups. The cost savings in the ambulatory blood pressure group (as a result of taking fewer medications and needing fewer physician visits) were offset by the higher cost of ambulatory monitoring. The changes in electrocardiographic and echocardiographic left ventricular mass were small and did not differ between the two groups.
The authors conclude that ambulatory blood pressure monitoring leads to less intensive antihypertensive treatment without a concomitant loss of blood pressure control or an increase in symptoms or left ventricular mass. Long-term prospective studies that include review of morbidity and mortality are warranted.
GRACE BROOKE HUFFMAN, M.D.
Staessen JA, et al. Antihypertensive treatment based on conventional or ambulatory blood pressure measurement: a randomized controlled trial. JAMA October 1, 1997; 278:1065-72.
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