Contamination of Botanical Dietary Supplements by Digitalis Lanata
In contrast to the specific fda requirements that drugs be shown to be safe and effective for each indication they receive, dietary supplements have no such stringent screening. The public often view dietary supplements as being free of risk because they are often touted as "natural." Two cases described in this report highlight the potential vagaries of such relatively unregulated substances.
The first case involves a previously healthy 23-year-old woman with clinical and EKG signs consistent with digitalis toxicity (nausea vomiting, lethargy, palpitations, and complete heart block on EKG). She was not known to be taking digitalis-related products, but had been ingesting a complex regimen of supplements reportedly to affect "internal cleansing of the body." Testing of these herbal preparations indicated the presence of cardiac glycosides, subsequently determined to be Digitalis lanata contaminating what had been intended to be simply plantain.
A second case involved a 46-year-old woman who had begun an almost identical herbal program, but became so ill after three days of the treatment that she sought local emergency care. Her symptoms and EKG findings also stimulated a search for digitalis toxicity, which was indeed the case. Both patients were discharged from the hospital several days later.
FDA investigation indicated that plantain contaminated with digitalis had been distributed around the United States for approximately two years. (The plantain under discussion is an herbal form, not the tropical banana plant found in consumer grocery stores). In both cases reviewed by the FDA, patients had ingested the same tradename product.
In a time when self-treatment products are abundantly used by our patients, clinicians must exercise renewed vigilance to detect adverse clinical effects potentially attributable to nonprescription products. Reporting of adverse clinical events to the FDA allows widespread dissemination of warning about potentially toxic products, as was done in these cases.
Slifman NR, et al. N Engl J Med 1998;339(12):806-811.
Competing Risk Analysis of Men Aged 55-74 years for Clinically Localized Prostate Cancer
As many as 200,000 men many be diagnosed with prostate cancer in the coming year, yet we lack data from large prospective randomized trials to present appropriate risk-benefit information to our patients who are uncertain about which method of treatment, including watchful waiting, to employ. Albertsen and associates used retrospective data on almost 800 men with localized prostate cancer who elected either not to be treated, or to be treated with hormonal therapy. Patients were followed for 15 years. All prostate cancers had Gleason scores at the time of diagnosis. Gleason scores range from 1-10, with lower scores indicating more differentiated tumors (low level of aggressiveness), and scores approaching 10 indicating poorly differentiated, much more aggressive tumors. An additional facet addressed by this trial was the long term follow-up (up to 20 years, in some cases) which allowed consideration of competing medical hazards that claimed mens lives. As long as Gleason scores were 4 or lower, death from prostate cancer was a minimal (risk of death 4-7% over 15 years). Men with Gleason scores greater than 7 suffer a much greater mortality risk from prostate cancer in the next 15 years (18-30%). These mortality rates are equally pertinent even when prostate cancer is diagnosed as late in life as age 74. Well differentiated tumors, as manifest by Gleason scores less than 4, are associated with minimal risk of prostate-related death in this long-term study.
Albertsen PC, et al. JAMA 1998;280:975-980.
The Diagnoses of Major Depression in Primary Care
At the same time as recent investigators have highlighted the morbid and mortal impact of depression, they have directed our attention to a relative infrequency of recognition of depression by primary care clinicians. Whether improving detection actually leads to improved outcomes, though intuitively appealing, remains unproven. To date, studies examining intensive screening and individualized clinician feedback in regards to elderly depressed patients have been unconvincing in demonstrating outcome benefit.
Klinkman et al studied practices of 50 southeast Michigan family physicians for a number of relevant factors to depression, including which factors are associated with misdiagnosis-either underdiagnosis (false negative) or overdiagnosis (false positive) depression. Clinician familiarity with the patient was strongly associated with identification of depression, and depression was uncommonly identified at the initial encounter. Patients most often diagnosed with depression incorrectly were likely to be suffering other mental health problems, or be undergoing treatment for major depression. In the latter case, successful treatment of depression relieved sufficient symptoms that patients no longer fulfilled DSM criteria for the diagnosis. These discrepancies suggest that clinicians are sensitive to patient cues of distress, and their diagnostic inaccuracies may reflect an appraisal of elements of subsyndromal depression.
Klinkman MS, et al Arch Fam Med. 1998;7:451-461
Clinical Scenario: The ECG shown in the Figure was obtained from a 42-year-old man complaining of atypical chest discomfort intermittently over the past few weeks. The patient was previously healthy. He was symptomatic at the time this tracing was recorded. What entities should be considered in your differential diagnosis? Is there evidence of atrial activity in the Figure?
Interpretation: There is a regular, supraventricular tachycardia (SVT) at a rate of just under 150 beats/minute. Practically speaking, the differential diagnosis of a regular SVT at this rate consists of three entities: 1.) sinus tachycardia; 2) atrial flutter; and 3) PSVT (paroxysmal supraventricular tachycardia). Definitive diagnosis is unfortunately not possible from this single tracing. The rhythm could be sinus tachycardia, with an upright P wave concealed withing the T wave seen in lead II. Atrial flutter should always be considered in the differential diagnosis of a regular SVT at a ventricular rate that is close to 150/minute—but the absence of any semblance of flutter activity in all 12 leads on this tracing makes this possibility less likely. Consequently, the most probable diagnosis is PSVT—which we strongly suspect because of the suggestion of subtle retrograde (negative) atrial activity that appears to be notching the terminal portion of the QRS complex in each of the inferior leads, and which produces a terminal positive deflection (simulating an r’) in lead V1.