Publications

OBJECTIVES

We sought to determine whether chronic conditions and functional limitations are equally predictive of mortality among older adults.

METHODS

Participants in the 1998 wave of the Health and Retirement Study (N=19430) were divided into groups by decades of age, and their vital status in 2004 was determined. We used multivariate Cox regression to determine the ability of chronic conditions and functional limitations to predict mortality.

RESULTS

As age increased, the ability of chronic conditions to predict mortality declined rapidly, whereas the ability of functional limitations to predict mortality declined more slowly. In younger participants (aged 50-59 years), chronic conditions were stronger predictors of death than were functional limitations (Harrell C statistic 0.78 vs. 0.73; P=.001). In older participants (aged 90-99 years), functional limitations were stronger predictors of death than were chronic conditions (Harrell C statistic 0.67 vs. 0.61; P=.004).

CONCLUSIONS

The importance of chronic conditions as a predictor of death declined rapidly with increasing age. Therefore, risk-adjustment models that only consider comorbidities when comparing mortality rates across providers may be inadequate for adults older than 80 years.

BACKGROUND

Human papillomavirus (HPV) testing is increasingly being used to determine the optimal cervical cancer screening interval in older women. Little is known about women's attitudes toward HPV testing or how these attitudes may influence medical discussions about cervical cancer screening.

METHODS

Preferences for HPV and concomitant Papanicolaou (Pap) testing were assessed through in-person interviews with diverse women aged 50 to 80 years recruited from community and university-based practices.

RESULTS

Eight hundred and sixty-five women (257 White, 87 African American, 149 Latina, and 372 Asian) were interviewed. Approximately 60% of participants wanted to be tested for HPV and another 15% would undergo testing if recommended by their physician. Among those wanting HPV testing, 94% would want more frequent than annual Pap tests if they had a positive HPV test and a normal Pap test. Two thirds of those under age 65 would be willing to switch to triennial Pap testing, and half of those aged 65 and older would be willing to discontinue Pap testing, if they had a negative HPV test and normal Pap test. Preferences for testing varied by ethnicity, age, place of birth, and cancer history.

CONCLUSIONS

The majority of older women were willing to use HPV testing to make decisions about frequency and duration of cervical cancer screening, but up to one third would want at least annual, ongoing screening regardless of HPV test results. Efforts should be made to ensure that HPV testing is used to reinforce appropriate utilization of screening tests.

Stress dramatically exacerbates pain in diseases such as fibromyalgia and rheumatoid arthritis, but the underlying mechanisms are unknown. We tested the hypothesis that stress causes generalized hyperalgesia by enhancing pronociceptive effects of immune mediators. Rats exposed to nonhabituating sound stress exhibited no change in mechanical nociceptive threshold, but showed a marked increase in hyperalgesia evoked by local injections of prostaglandin E(2) or epinephrine. This enhancement, which developed more than a week after exposure to stress, required concerted action of glucocorticoids and catecholamines at receptors located in the periphery on sensory afferents. The altered response to pronociceptive mediators involved a switch in coupling of their receptors from predominantly stimulatory to inhibitory G-proteins (G(s) to G(i)), and for prostaglandin E(2), emergence of novel dependence on protein kinase C epsilon. Thus, an important mechanism in generalized pain syndromes may be stress-induced coactivation of the hypothalamo-pituitary-adrenal and sympathoadrenal axes, causing a long-lasting alteration in intracellular signaling pathways, enabling normally innocuous levels of immune mediators to produce chronic hyperalgesia.

Erythrocytes containing primarily hemoglobin S (SS RBCs) are abnormally adherent. We now know that SS RBCs express numerous adhesion molecules, and that many of these can undergo activation. SS RBCs exposed briefly to epinephrine show markedly increased adhesion to both laminin and endothelial cells. In vivo, infusion of epinephrine-activated but not unstimulated SS RBCs causes RBC adhesion, vaso-occlusion, organ trapping, and shortened RBC survival in the circulation. Epinephrine treatment of SS RBCs before infusion also induces adhesion of murine leukocytes to vascular walls. Indeed, in vitro, SS RBCs can activate leukocyte adhesion and cytokine production. We now have demonstrated both in vitro and in vivo evidence for the importance of RBC signaling and have also shown that SS RBC adhesion is determined by genetic polymorphisms in the signaling pathway that activates adhesion. These advances will hopefully lead to new therapeutic modalities for sickle cell disease.