Orlistat in the Long-Term Treatment of Obesity in Primary Care Settings

Source: Hauptman J, et al. Arch Fam Med 2000;9:160-167.

Obesity is a problem in about 30% of the U.S. population, but few successful long-term strategies have been identified. Recently, focus has been shifted from achievement of ideal body weight to achievement and maintenance of a 5-15% reduction in body mass index (BMI), which translates into meaningful improvements in traditional cardiovascular risk factors. Most studies of pharmacotherapy for obesity have been short term and have studied populations in non-primary-care settings. This report details a primary-care-setting study of obese persons (BMI ³ 30) who were treated with diet combined with orlistat 60 mg or 120 mg thrice daily for two years (n = 635).

The larger dose of orlistat produced a 7.9% decrease from initial body weight, compared with a 4.2% decline in the placebo group at the one-year mark (both groups received dietary intervention). Maintenance of weight loss was significantly better for orlistat recipients than placebo. Approximately half of orlistat-treated patients lost at least 5% of their initial body weight by one year, compared with 30.7% in the placebo group. Lipid levels and blood pressure were favorably affected by drug treatment.

Tolerance of treatment was excellent; rates of withdrawal due to adverse events were not statistically different between placebo and treatment groups. GI effects, the most frequent adverse experience, were generally transient and mild to moderate, resolving without intervention.

Orlistat is effective and well tolerated over the long term in the primary care setting.

Dissociation in Near-Death Experiences

Source: Greyson B. Lancet 2000; 355:460-463.

The term dissociation has been described as "a separation of thoughts, feelings, or experiences from the normal stream of consciousness and memory." The ranges of this experience extend from simple daydreaming to multiple personalities. Dissociation is not always considered pathologic and has been described in victims of trauma, rape, or other intense emotional/physical assault.

Near-death experiences (NDE) are often described as a perception of having left the physical boundary and transcending time/space boundaries. It has been suggested that NDE are, in fact, dissociations. Greyson studied the frequency of dissociation among people who reported NDE, comparing this with the frequency of dissociation in persons who had been close to death but did not experience NDE. The instrument used to measure dissociation was the dissociative experiences scale (DES), a 28-item visual analog scale measuring a variety of different dissociative experiences.

Evaluation of 134 individuals who reported having been close to death determined that 72% described NDE. Scores on the DES for persons experiencing NDE were significantly higher than for individuals who had not experienced NDE, but the DES scores were not as high as those seen in persons with pathologic dissociative disorders. Greyson concludes that NDE are not a manifestation of a dissociative disorder, nor are they a pathological type of dissociation.

Oral Androstenedione Administration and Serum Testosterone Concentrations in Young Men

Source: Leder BZ, et al. JAMA 2000; 283:779-782.

Androstenedione (ansd) has recently become popular among the lay public for (unsubstantiated) claims that it will have anabolic effects similar to those of anabolic steroids, reportedly increasing testosterone levels. Since ANSD is available over the counter as a dietary supplement, substantial numbers of individuals may be using it in an attempt to enhance athletic ability, without proof of efficacy. The current study examined the effect of 100-300 mg per day ANSD orally on testosterone levels in healthy young men (n = 42). Measured responses included testosterone, estradiol, estrone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex-hormone-binding globulin (SHBG).

Serum testosterone was significantly increased by the 300-mg ANSD dose, but not by the 100-mg dose. Both ANSD doses significantly increased estradiol and estrone levels. Other measured markers did not change with ANSD supplementation. This study documents that short-term administration of higher doses (at least 300 mg) of ANSD is associated with increased levels of testosterone. Such elevations in women could have virilizing effects; in men, the elevated estrogen could also have feminizing effects (e.g., gynecomastia); in children, premature epiphyseal closure due to supraphysiologic amounts of gonadal steroids could lead to reduced ultimate height.

Awareness During Anaesthesia: A Prospective Case Study

Source: Sandin RH, et al. Lancet 2000;355:707-711.

Patient recall of events occurring while under operative general anesthesia is traditionally regarded as a rare event, reportedly occurring in fewer than 1% of individuals. On the other hand, patient concern about pain or other stressful experiences under anesthesia is commonplace, with as many as half of patients reporting such concerns. Sandin and colleagues did a prospective evaluation of patient recall of awareness during surgery by personal interview of adults older than 15 years of age (n = 11,785) who received general anesthesia in two Swedish hospitals. Interviews were taken, immediately postoperatively, at days 1-3 and days 7-14 postoperatively.

Only 18 women and seven men (slightly < 0.2% of the total evaluated population) reported introanesthesia awareness. The most common underlying factor in reported awareness was the use of neuromuscular block during surgery. Patients who did not receive neuromuscular block did not report intraoperative awareness. Additionally, more than half of persons reporting operative awareness had previously experienced a similar phenomenon. Whether monitoring techniques designed to detect intraoperative awareness will actually reduce this experience will be difficult to determine, since 50,000 patients would be needed to demonstrate a halving of intraoperative awareness from the demonstrated level in this study of less than 0.2%.

Meta-Analyses of the Relation Between Silicone Breast Implants and the Risk of Connective Tissue Disease

Source: Janowsky EC, et al. N Engl J Med 2000;342(11):781-790.

Alleged association of silicone breast implants (SBI) with a variety of consequences, including connective tissue/autoimmune diseases, has sparked substantial medical and legal debate. Though three other meta-analyses of breast implants exculpated them, study characteristics were felt to still leave the issue inconclusive. Janowsky and colleagues performed a meta-analysis specifically to conclusively address whether SBI is associated with these adverse outcomes. Substrate for their report included 20 different studies.

No evidence of an association between SBI and connective tissue diseases was discerned. A trend toward increased risk of Sjogren’s syndrome was not statistically significant. One method of analysis suggested that the frequency of all connective tissue diseases combined, and Sjogren’s syndrome, was slightly elevated, though the clinical relevance of this increase appears dubious. With the exception of the effect induced by a single study, which, when included, suggests a minimal increased risk, Janowsky et al demonstrate that data accrued thus far do not support any important relationship between SBI and connective tissue diseases.

Causes and Severity of Ischemic Stroke in Patients with Internal Carotid Artery Stenosis

Source: Barnett HJ, et al. JAMA 2000;283:1429-1436.

Carotid stenosis (cs) is a common concomitant of stroke. In persons with demonstrated CS, the likelihood of subsequent stroke referable to that stenosis has been poorly defined. Barnett and colleagues followed 2885 patients for five years who had been determined to have more than 70% symptomatic CS, delineating the underlying pathology of subsequent stroke. The population was derived from the North American Symptomatic Carotid Endarterectomy Trial, a study spanning the 1987-1997 interval.

As anticipated, most stroke was ischemic in origin (more than 95%). Large-artery stroke was more than twice as frequent as cardioembolic and lacunar etiologies combined. In carotid arteries demonstrating 70-99% stenosis, as many as 20% of subsequent strokes are not apparently related to the underlying ipsilateral carotid disease. Final treatment strategies should take into account that carotid surgery alone does not entirely eliminate risk of subsequent stroke; incorporation of knowledge about the patients’ subsequent risk for lacunar and cardioembolic stroke is essential for maximum risk reduction.