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Source: Inciardi JF, et al. Am J Med 2000;109:277-281.
Clinicians use a variety of tools to screen for colorectal cancer, including rigid sigmoidoscopy, flexible sigmoidoscopy, and colono-scopy. Success of such methods is predicated upon tumors being resectable and within the reach of the tool used. There has been literature support for the observation that tumor geography is shifting such that "left-sided" tumors (i.e., located in the sigmoid colon and more distal, excluding the anus) are becoming less frequent, and "right-sided" tumors (i.e., proximal to the sigmoid colon) more common. Flexible sigmoidoscopy, which detects left-sided tumors, maintains its viability only so long as a sufficient proportion of disease burden remains within the 65 cm range. If tumor burden geographically shifts sufficiently, choice of screening tool will be directly affected.
The purpose of the current study was to examine, by means of analysis of the California State Cancer Registry, the incidence of left-sided and right-sided colon cancers. It would be anticipated that sigmoidoscopy would favor reduction in incidence of left-sided cancers.
Overall, colorectal cancer incidence decreased steadily by 19% over 10 years, but left-sided cancers decreased more than twice as much as right-sided tumors. A good deal of this left-sided cancer reduction is attributed to sigmoidoscopic screening and subsequent tumor resection. Inciardi et al posit that the increased frequency of right-sided colorectal cancers should stimulate consideration of modification of screening processes, in essence to more frequently use colonoscopy as the routine screening tool.
Source: Chesnut CH, et al. Am J Med 2000;109:267-276.
The public health as well as personal effect of osteoporosis (OSPS) and its sequelae remains abundant. The last five years have seen a proliferation of available tools to combat and prevent this disorder, including agents shown to effectively reduce fractures in subjects at risk for glucocorticoid-induced OSPS in both genders. Calcitonin (CTN) has demonstrated an ability to decrease bone resorption and improve or stabilize bone mineral density (BMD) in osteoporotic patients. Since BMD is a surrogate end point, and the patient and clinician alike are ultimately concerned with fracture reduction efficacy, the issue that no large, randomized, prospective trial of CTN for fracture reduction has been performed may have been a limiting factor in therapeutic selection of this agent for treatment of OSPS. To that end, the Prevent Recurrence of Osteoporotic Fractures (PROOF) study (n = 1255) was undertaken.
Subjects were randomized to receive either calcitonin nasal spray at doses of 100-400 IU daily, or placebo, in addition to 1000 mg/d calcium supplements and 400 IU vitamin D daily. Inclusion criteria were postmenopausal status, and presence of either vertebral fractures or BMD greater than 2 standard deviations below normal. Patients were followed for five years.
Use of CTN (200 IU/d) resulted in a 33% reduction in new vertebral fractures, even in persons without a major effect on BMD. Whether CTN reduces fracture through decreased bone turnover, improved bone quality, improved bone strength, improved bone mineralization, or some combination of such factors remains to be determined.
Source: Hujoel PP, et al. JAMA 2000;284:1406-1410.
Atherosclerosis, at its most fundamental level, is felt to be an inflammatory disease. Much attention has recently been focused upon the associations observed between disorders like periodontitis and gingivitis with cardiovascular end points such as myocardial infarction (MI). Since MI, gingivitis, and periodontal disease all occur with increasing age, increased duration of smoking, and increased body fat, it has been unclear whether the association of oral disorders and coronary disease is causal, or merely concomitant.
In order to better define this relationship, Hujoel et al studied data from the 1971-1975 NHANES 1 study (n = 8032). Addressing status of participants for the presence or absence of periodontitis or gingivitis at baseline, the population of adults age 26-74 who were followed through 1992 in whom a first MI occurred. Each of the participants underwent a general history and physical examination, laboratory tests, and a dental examination.
Gingivitis at baseline was not associated with cardiovascular risk; the presence of periodontitis was associated with a trend toward greater coronary heart disease, but this association did not achieve statistical significance. Since this study is the largest to date to address this issue, it is felt that the association of poor oral health with cardiovascular end points, if any, must be small. On the other hand, even if the absolute contribution to cardiovascular risk is small since periodontitis is a common disorder, future studies addressing larger populations might better delineate the potential for effect on end points like MI.
Source: Hayden FG, et al. N Engl J Med 2000;343:1282-1289.
Influenza (flu) remains a major source of morbidity and mortality in the United States, despite the widespread availability of vaccine and antiviral pharmacotherapies. Prevention of influenza by antiviral drug therapy has, until quite recently, been limited by the fact that amantadine and rimantadine are only efficacious against influenza A. Two new neuraminidase inhibitors—zanamivir and oseltamivir—are not only effective against both influenza A and influenza B, but in contrast to prior antiviral drug use, they have not been thus far associated with emergence of drug-resistant influenza strains.
At the time of this writing, only oseltamivir (Tamiflu) is approved for prophylaxis of influenza. This study used zanamivir (Relenza) in an attempt to reduce family member influenza in a large group of subjects (n = 321) who developed an influenza-like illness (ILI) during the 1998-1999 flu season.
Once an index case came down with an ILI, either zanamivir 10 mg qd (by inhalation) or placebo was given to household contacts for 10 days. The index case was treated with the therapeutic FLU dose, 10 mg b.i.d. for five days.
There was a striking difference in the frequency with which previously healthy household contacts came down with ILI if they received zanamivir: 4% vs. 19% on placebo. No serious adverse events occurred.
Zanamivir, in a standard dose administered by inhalation once daily, appears to be an effective and safe intervention for prevention of influenza A and B; its efficacy for treatment of FLU has been previously established.
Source: Peterson JG, et al. Am J Med 2000;109:371-377.
When used individually, both aspirin (ASA) and angiotensin-converting enzyme inhibitors (ACEIs) have shown a favorable secondary prevention effect among patients with ischemic heart disease. Intuitively, one would expect that the combination of these agents might produce even greater advantage. On the other hand, ASA has been shown to antagonize the hemodynamic effects of ACEI in hypertension, and retrospective studies have intimated that ASA might reduce ACEI benefits in persons with heart failure. The current report analyzed the effect of ASA when combined with ACEI (ASA/ACEI) on mortality in a large trial of patients with coronary artery disease who had been treated as part of the GUSTO-I trial (n = 41,021) and the EPILOG trial (n = 2619). The analysis was retrospective; no prospective trials to assess the effect of ASA/ACEI on morbid or mortal end points have been performed.
In the GUSTO trial, ASA/ACEI use was associated with a statistically significantly greater unadjusted mortality rate than ASA alone; however, ACEI-treated patients had more hypertension and anterior MI at baseline. In the EPILOG trial, the ASA/ACEI group also showed a greater unadjusted mortality rate than ASA alone. Even after multivariate analysis adjusted for potential confounders, ASA/ACEI treatment appeared to be associated with an increased hazard risk of death. One of the mechanisms by which ASA is described to compete with beneficial effects of ACEI is that bradykinin, which is enhanced by ACEI, stimulates vasodilatory prostaglandins. ASA inhibits such prostaglandins.
Because the study is observational, causality between ASA/ACEI and adverse outcome has not been conclusively established. However, such observational information should prompt the formulation of a prospective randomized trial to resolve the issue.
Source: Dawson DL, et al. Am J Med 2000;109:523-530.
Medical therapies for intermittent claudication (IC) are few. Pentoxifylline (PTF) was the only approved agent from 1984-1999. Recently, cilostazol (CSL) has been added to the therapeutic choices. It has been shown to be effective for improvement in walking distance on a treadmill; additionally, IC patients report improved physical function when treated with CSL.
Patient selection for this double blind placebo-controlled trial of PTF vs. CSL (n = 539) included the presence of stable IC for at least six months, documentation of peripheral arterial disease (post-exercise ankle pressure reduced at least 20 mm Hg, or at least 10 mm Hg with an abnormal ankle/brachial index), and ability to adequately complete treadmill testing. Patients were evaluated at baseline and monthly for six months of treatment (CSL 100 mg B.I.D., PTF 400 mg T.I.D., or placebo). All patients received three doses daily (i.e., CSL treatment included 1 "dummy" capsule) to maintain the double-blind status of the trial.
By week four of evaluation, and continuing through the conclusion of the trial, CSL-treated patients enjoyed a statistically significant increase in maximal treadmill walking distance when compared to placebo or PTF. Improvements in patients treated with PTF were not superior to placebo. Overall, all treatments were well tolerated, though headache and diarrhea were morse frequent in CSL-recipients.
Previous reports have brought the clinical efficacy of PTF into question. The efficacy of CSL appears to be well substantiated.