Psychological Response and Breast Cancer Survival

Source: Watson M, et al. Lancet; 1999;354:1331-1336.

Though a role for the psychological status of patients and outcome of cancer has been hypothesized for some time, studies to date have been inconclusive or hampered by small size or short follow-up. One study, which did demonstrate an effect, indicated that women who were described as possessing a "fighting spirit" as opposed to "helpless" were significantly more likely survivors of breast cancer at both five- and 10-year marks. However, because the study was small (n = 57), did not adjust for baseline lymph node status, and used a psychological interview rather than a detailed, validated psychometric instrument for assessment, the issue is far from conclusively resolved.

Watson and colleagues used the mental adjustment to cancer (MAC) and Courtauld emotional control (CEC) scales for evaluation, women were followed for a minimum of five years, and a large population of women (n = 578) was enrolled.

Cancer relapse occurred in 27% of women at an average interval of two years. No significant effect of psychological response was evident on either overall or event-free survival. Of the measured issues on the MAC, the subgroup area with a high level of helplessness or hopelessness was found to have a significantly higher likelihood of death at five years, but the "fighting spirit" was not associated with improved survival. Watson et al opine that clinicians should be more cautious in their suggestion of benefits achieved by "maintaining a fighting spirit." Indeed, they note that sometimes women may feel guilty when maintaining a fighting spirit becomes difficult or impossible; it may be possible for clinicians to relieve patients of some of this burden.

Interferon Gamma, Low-Dose Prednisolone, and IPF

Source: Ziesche R, et al. N Engl J Med 1999;341:1264-1269.

Survival in idiopathic pulmonary fibrosis (IPF) is poor, averaging only 4-5 years. Among patients who receive oral glucocorticoids, the standard treatment for IPF, fewer than one-third improve. Though the mechanisms inducing the disorder are not understood, it is typified by progressive proliferation of populations of fibroblasts that deposit collagen in the lung interstitium. Since interferon gamma has been shown to inhibit lung fibroblast growth, it has been a sensible candidate for trial in IPF.

Ziesche and associates studied 18 patients with IPF who had failed to respond positively to traditional therapies, including 50 mg/d of oral prednisolone for one month. Patients were assigned to receive either 200 mcg of interferon gamma-1b thrice weekly subcutaneously plus oral prednisolone (7.5 mg/d) or the same dose of prednisolone alone, for one year.

Only in patients who received interferon were positive changes in ventilation, gas exchange, and total lung capacity seen. Overall, prednisolone-alone recipients showed a 4% decline in total lung capacity, compared to a 9% improvement in recipients of interferon plus steroid.

Interferon resulted in substantial improvements in partial pressure of arterial oxygen at rest and during exercise, requirement for supplemental oxygen, and ability to perform activities of daily living.

Initial treatment is problematic in that patients predictably exhibit fever, chills, and muscle pain, but these effects diminish over the first 9-12 weeks of treatment. These early results provide encouraging news about interferon as an effective treatment for IPF. 

Sleep Debt on Metabolic and Endocrine Function

Source: Spiegel K, et al. Lancet 1999;354:1435-1439.

In the early part of this century, average amount of nightly sleep was nine hours; as this century closes, we average only 7.5 hours of nightly sleep due to increased time demands of both work and leisure activities. Claims have been made that since only 4-5 hours per night represent "core sleep," persons might progressively reduce their total sleep hours without compromising these essentials, but studies to examine the effects upon vigilance and mood subsequent to revision of sleep time by 2-3 hours have been conflicting.

Spiegel and colleagues studied healthy subjects (n = 11) in a sleep laboratory, varying sleep nightly from 4-12 hours over 16 days. The first three nights held eight hours of sleep, followed by six nights of four hours’ sleep, concluding the study with seven nights of 12 hours’ sleep. Periodic measurements of saliva for cortisol and glucose tolerance tests were done.

REM sleep was significantly reduced during periods of sleep deprivation, calling into question the wisdom that sleep time can be reduced while maintaining core sleep time. During times of sleep deprivation, glucose tolerance was significantly impaired. Also, cortisol elevations were evident during sleep deprivation periods.

Spiegel et al suggest that sleep deprivation has demonstrable endocrine and metabolic consequences. The long-term effects of such alterations remain unknown.

Old and New Anti-Hypertensive Drugs in Elderly Patients

Source: Hansson L, et al. Lancet 1999;354:1751-1756.

The swedish trial in old patients with Hypertension (STOP-Hypertension study), published in 1991, was one of the first reports to convincingly establish that beta-blocker and diuretic therapies were efficacious in achieving reductions in cardiovascular morbidity and mortality in elderly patients. STOP-2 is a trial begun in 1992 to compare "newer drugs" (e.g, ACE inhibitors, calcium channel blockers) with "conventional" treatment (e.g, diuretics, beta-blockers). Since conventional treatment has been shown to reduce important endpoints, it was felt unethical to include a placebo group.

During a two-year period, adults (n = 6628) with sustained blood pressure more than 180/105 were randomized to conventional therapy vs. ACE inhibitors or calcium channel blockers (approximately 2000 participants in each group). ACE inhibitors included lisinopril and enalapril, calcium antagonists included felodipine or isradipine, and diuretics/beta blockers included atenolol, metoprolol, pindolol, HCTZ, or an HCTZ/amiloride combination. Patients were followed up to six years.

Almost half of the patients required more than one drug for blood pressure control, but in the monotherapy-successful groups, equal levels of blood pressure lowering were achieved for each drug treatment.

Fatal cardiovascular events occurred with equal frequency in all drug treatment groups, though frequency of MI and CHF were significantly lower in persons receiving ACE inhibitors than calcium channel blockers. Hansson and colleagues conclude that older and newer antihypertensive drugs are equally efficacious in treatment of hypertension; therapeutic choice, based upon these data, will rest upon cost, tolerability, and coexisting disorders.

Use of Advance Directives by Community-Dwelling Older Adults

Source: Kvale JN, et al. J Clin Outcomes Man 1999;6(1):39-43.

Since 1990, subsequent to the self-Determination Act, health care facilities participating in Medicaid or Medicare must inform patients in writing about their rights in reference to advance directives (i.e., wishes of the patients about their medical care when they are seriously ill or near death and may not be able to directly communicate their express interests). This Act is focused specifically on inpatient populations, but sentiment for expanding to the ambulatory setting is growing. This study looked at free-living, noninstitutionalized older adults to assess the level of planning for future care.

Study subjects (n = 571) completed a telephone interview during which they were essentially asked three questions based upon the type of medical care they would want (or not want) in the event they were ill and unable to make decisions for themselves: 1) Have you talked to someone about this issue?; 2) Have you talked to your doctor about this issue?; 3) Have you made written plans for this possibility?

Almost half the respondents had participated in a discussion of this issue with someone, but only 13.5% had used a physician in this regard, and only 16.1% had written plans.

The failure of the physician to initiate discussion about advance directives is commonly noted as a primary stumbling block in its accomplishment. Physicians who find merit in advance directives for their patients have great opportunity for enhancing this channel of interaction.

Elevated C-Reactive Protein Levels in Overweight and Obese Adults

Source: Visser M, et al. JAMA 1999; 282:2131-2135.

Though previously regarded as a fairly passive storage depot, the fat compartment is now known to produce such compounds as interleukin-6, ultimately being responsible for as much as 25% of IL-6 made each day. IL-6 is a stimulant of local and systemic inflammation, and promotes hepatic acute-phase protein generation.

CRP is an acute-phase protein predictive of risk of coronary heart disease, MI, ischemic stroke, and peripheral arterial disease. Visser and associates sought to elucidate the relationship between overweight, obesity, and serum CRP.

From the National Health and Nutrition Examination Survey (NHANES III) population, a sample (n = 16,616) of individuals had BMI measured in conjunction with CRP. Most healthy individuals have a CRP level that is undetectable (designated < 0.22 mg/dL, the lower limit of detection by currently available measurement tools); clinical elevation of CRP is considered a level > 1.00 mg/dL. Patients with disorders known to influence CRP (e.g., rheumatoid arthritis) were excluded from the trial.

Prevalence of detectable CRP levels rose as BMI increased in both genders. Frankly elevated CRP levels were 2-6 times more common among obese individuals than their normal weight counterparts. Visser et al conclude that these data suggest a state of low-grade inflammation in overweight and obese persons.