Clinical Briefs in Primary Care
Absence of Benefit of Eradicating H. pylori in Patients with Nonulcer Dyspepsia
Source: Talley NJ, et al. N Engl J Med 1999;341:1106-1111.
Most upper abdominal discomfort (dyspepsia) does not arise from peptic ulcer disease but is due to as-yet-unexplained derangements. In the course of evaluation for dyspepsia symptoms, most ulcer disease that is not NSAID-induced is secondary to Helicobacter pylori infection, and about 30% of patients who emerge with a diagnosis of nonulcer dyspepsia harbor this pathogen. Several trials have attempted to determine whether Helicobacter eradication influences clinical outcome in nonulcer dyspepsia; unfortunately, contradictory results and flawed methodology have precluded a conclusive answer.
The currently reported study reflects a one-year evaluation of Helicobacter-positive adults (n = 337) with nonulcer dyspepsia, treated with twice-daily omeprazole, amoxicillin, and clarithromycin vs. placebo. Endoscopic studies confirmed that these patients were not sufferers of esophagitis, Barrett’s esophagus, ulcers, erosions, or carcinoma. Dyspepsia was rated using the Gastrointestinal Symptom Rating Scale of 0 (no symptoms) to 6 (very severe symptoms).
Urea breath testing indicated that 90% of patients were free of Helicobacter at 4-6 weeks, and 80% remained so at the 12-month conclusion of the trial. Eradication of Helicobacter did not appear to influence symptomatology. Whether long-term Helicobacter infection merits treatment for reasons other than symptomatology or ulcer disease remains a hotly debated issue. These data suggest that treatment of Helicobacter, in an attempt to resolve nonulcer dyspepsia, is ineffectual.
Fruit and Vegetable Intake in Relation to Risk of Ischemic Stroke
Source: Joshipura KJ, et al. JAMA 1999;282:1233-1239.
Although epidemiologic data are supportive of enhanced intake of fiber, potassium, and antioxidants for prevention of cardiovascular disease, few data are available specifically relating fruit and vegetable intake to cardiovascular end points. The study population assessed in this report, composed of participants in the Nurses’ Health Study and Health Professionals Follow-up Study, was distinctly larger (n = 112,279) than in any previous investigation. End points examined included the relationship of specific fruits and vegetables, and overall fruit and vegetable intake, to ischemic stroke.
There was an inverse relationship between overall fruit and vegetable intake and ischemic stroke. Comparing the highest quintile of intake to the lowest, there was a 0.69 relative risk overall, subgrouped into 0.74 (women) and 0.61 (men), despite the fact that the median daily intake of total fruits and vegetables was consistently higher for women than men (5.8 vs 5.1 servings daily). For each additional daily serving of fruit, there was an associated 7% lower risk of ischemic stroke for women and 4% for men.
Cruciferous vegetables (such as broccoli, brussel sprouts, cabbage, and cauliflower), green leafy vegetables, and citrus fruits were associated with lowest risk. No single fruit or vegetable stood out as distinctly superior to another for its protective effect. Joshipura and colleagues conclude that these data support the recommendation to consume at least five servings of fruits and vegetables daily.
Calcium and Magnesium in Drinking Water and the Risk of Death from Hypertension
Source: Yang C, Chiu H. Am J Hypertens 1999;12:894-899.
A relationship between public water supply calcium and magnesium content (known as water hardness’) and cardiovascular mortality has been detected in more than one observational study. In Taiwan, where hypertension is recognized as one of the 10 most common causes of death in men and women, there is definite geographic variation in hypertension mortality, suggesting that environmental factors may play a role. This study evaluated the relationship between water hardness and death from hypertension (n = 2336) in a variety of geographically distinct districts from 1990 to 1994.
Subjects were stratified into quintiles by level of drinking water calcium and magnesium; a comparison was made between water hardness in controls vs. persons succumbing to hypertensive sequelae.
Water calcium content was inversely associated with hypertension death risk, and significantly so for persons in the top two quintiles vs. the lowest. Similarly, when compared with the lowest quintile, people in the highest quintile intake of magnesium in drinking water were at a 20% less odds ratio of hypertension-related death.
Bed Rest: A Potentially Harmful Treatment Needing More Careful Evaluation
Source: Allen C, et al. Lancet 1999; 354:1229-1233.
Generations of healers have believed in the therapeutic benefits of bed rest, including commentary by Hippocrates himself. Through the 1800s, with few efficacious tools at hand, bed rest was a primary treatment for many disorders. Contrary to this time-honored wisdom, consequences like DVT, osteoporosis, pressure sores, contractures, and atrophy have all been ascribed to bed rest. Only a few areas of medicine have specifically examined the role of bed rest as a therapeutic modality.
Allen and colleagues were able to identify 39 randomized trials referable to 15 different disorders such as bed rest for post-lumbar puncture, radiculography, cardiac catheterization, liver biopsy, low back pain, labor, threatened abortion, myocardial infarction, and rheumatoid arthritis.
Among 24 trials of bed rest after a medical procedure, none demonstrated significantly improved outcome, though a number did show statistically significantly worse outcome. Even in trials of spinal headache post-lumbar puncture, no significant benefit of bed rest was discernible. No benefit of bed rest is demonstrated for acute low back pain, myocardial infarction, tuberculosis, or hepatitis. Similarly, obstetrical trials not only show no improvement when bed rest is employed in first-stage labor, they actually show worse outcomes.
That bed rest is of questionable value has not seemed to effect change among clinicians. Seventeen years after the publication of a trial on the absence of benefit from bed rest after lumbar puncture, 80% of neurologists in the United Kingdom continued to insist upon the practice. Scientifically substantiated indications for bed rest remain to be defined.
Exogenous Reinfection as a Cause of Recurrent Tuberculosis After Curative Treatment
Source: van Rie A, et al. N Engl J Med 1999;341:1174-1178.
Tuberculosis occurring many years after primary infection is called post-primary TB. Previous to the availability of DNA fingerprinting, it was unclear whether post-primary TB was a consequence of reactivation of endogenous primary disease or reinfection, though traditional opinion held that endogenous reactivation was the primary method. With currently available tools, it is now possible to discern whether post-primary TB is caused by the same strain that was etiologic for the primary infection or another strain.
The population studied, from Cape Town, South Africa, reflects a high number of cases of TB per year (1000 cases per 100,000 population per year). Subjects sustained at least two episodes of post-primary TB within a six-year period. These patients were all HIV negative, free from diabetes, end-stage renal disease, or other immunosuppressive disorder.
A different DNA pattern than had been causative of the primary infection was reported in 75% of post-primary TB cases. Twenty-five percent of post-primary TB involved drug-resistant strains, of which half were due to exogenous reinfection and half due to endogenous reactivation.
Since, in this population, most post-primary TB is a result of exogenous reinfection, van Rie and colleagues suggest additional emphasis on early case detection to prevent exposure to active disease in those with cured primary TB. It is unknown whether these data will be reflective of post-primary TB etiologies in settings with less prominent background disease rates, where opportunity of exposure to new active cases is substantially less.
HIV-1 Drug Resistance in Newly Infected Individuals
Source: Boden D, et al. JAMA 1999;282:1135-1141.
As many as half of hiv-1 infected individuals treated with antiviral therapy may develop resistance. Contributing factors include serial monotherapy, uninhibited viral replication due to inadequate suppression by less than maximally effective agents, difficulty adhering to complicated regimens often associated with substantial burden of side effects, and therapy begun late in the course of the disease. Transmission of multidrug-resistant HIV-1 virus is a serious concern. To evaluate the demographics of this problem, Boden and associates evaluated mutations in 80 newly HIV-1 infected individuals who acquired the disease between July 1995 and April 1998; during this time, multidrug treatment of HIV had become the standard methodology.
More than 16% of samples analyzed demonstrated resistance to one or more antiretroviral agents and almost twice that number showed a three-fold or greater reduction in susceptibility to at least one retroviral agent. Only about 4% of samples demonstrated multidrug resistance.
Study subjects in this group came primarily from a population of urban homosexual men. Hence, demographics here described may not reflect other community settings and may not be applicable to women or heterosexual men. Boden et al suggest that clinical trials that evaluate potential virological and immunological benefits achieved by using resistance assay-guided therapeutic regimens are in order.
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