Publications

BACKGROUND

The accuracy of a woman's perception of her risk of developing breast cancer has gained importance as more options for primary prevention have become available for those at increased risk. Conversely, women at average risk who perceive themselves as at increased risk may suffer from avoidable anxiety or unnecessary treatment. This study examined characteristics associated with perception of breast cancer risk among women at average and increased risk.

METHODS

We included 1700 women 40-74 years old without a history of breast cancer. The outcome variable was a woman's perceived lifetime risk of developing breast cancer. The Gail model was used to categorize a woman's actual risk as average or high. Multivariate logistic regression models were used to model a woman's perception that her risk was (1) higher than average for those whose Gail score indicated average risk (<1.67% 5-year risk) and (2) accurate for those whose Gail score indicated increased risk (> or = 1.67% 5-year risk).

RESULTS

Of women at average risk, 72%, but only 43% of those at high risk, accurately perceived their risk. Among women at average risk, those who were younger, had a family history of breast cancer, had no history of childbirth, or had more frequent exposure to lay media information about breast health were more likely than women without these characteristics to overestimate their future risk. Among women at increased risk, younger women and those with a family history of breast cancer were more likely than women without these characteristics to accurately perceive their increased risk. African American women were less likely than white women to accurately perceive their risk.

CONCLUSIONS

A majority of women at high risk of developing breast cancer underestimate their risk, and a substantial proportion of women at average risk perceive they are at increased risk.

OBJECTIVE

To determine whether race is associated with outcomes of inpatient stroke rehabilitation.

DESIGN

Retrospective cohort study.

SETTING

A community-based inpatient rehabilitation facility.

PARTICIPANTS

Poststroke patients (N=1002) admitted to a community-based inpatient rehabilitation facility between 1995 and 2001.

INTERVENTIONS

Not applicable.

MAIN OUTCOME MEASURES

Functional improvement at discharge from the rehabilitation facility, discharge disposition, and functional improvement at 3 months after discharge. Inpatient and follow-up data were collected from the facility's electronic patient database. We used the FIM instrument to assess functional status at admission, discharge, and follow-up.

RESULTS

In multivariable models, blacks achieved less functional improvement at discharge (-1.9 FIM points, P=.02) compared with whites and, despite worse FIM scores, were more likely to be discharged to home (adjusted odds ratio=1.7; 95% confidence interval, 1.1-2.5). Although Asian-American patients did not differ from whites in terms of functional improvement at discharge or disposition, they had less improvement at 3 months following discharge (-6.3 FIM points, P=.005).

CONCLUSIONS

We identified racial disparities in poststroke outcomes in a community-based inpatient rehabilitation facility. Future research in stroke rehabilitation should explore the consistency of these findings across settings and if they are confirmed, identify explanatory mediators to better inform efforts to eliminate racial disparities.

The Medicare Modernization Act of 2003 authorized the most sweeping changes to the Medicare and Medicaid programs since their inception in 1965. One key feature, a prescription drug benefit, will begin enrolling seniors in November 2005, and the benefit will begin in January 2006. This benefit will have complex and largely unknown effects on medication adherence in the elderly. It has a complex system of copayments and deductibles and subsidy eligibility requirements, as well as a "donut hole." Drug coverage for people dually eligible for Medicare and Medicaid will change greatly. Medicare beneficiaries will have to choose from a large, bewildering choice of prescription plans and many will turn to their physicians for advice. This article details the background, benefits, and expected impact of all of these aspects of the new Medicare Part D prescription drug benefit.

BACKGROUND

Regulatory T cells have been proposed to play an important role in regulating allergic inflammation. The transcription factor Foxp3 is a master switch gene that controls the development and function of natural and adaptive CD4(+)CD25(+) regulatory T (T(R)) cells. In human subjects loss-of-function Foxp3 mutations trigger lymphoproliferation, autoimmunity, and intense allergic inflammation in a disease termed immune dysregulation polyendocrinopathy enteropathy-X-linked syndrome.

OBJECTIVE

We sought to examine the evolution and attributes of allergic inflammation in mice with a targeted loss-of-function mutation in the murine Foxp3 gene that recapitulates a known disease-causing human Foxp3 mutation.

METHODS

Foxp3 mutant mice were generated by means of knock-in mutagenesis and were analyzed for histologic, immunologic, and hematologic abnormalities. The role of signal transducer and activator of transcription 6 (Stat6) in disease pathogenesis was analyzed by using Stat6 and Foxp3 double-mutant mice.

RESULTS

Foxp3 mutant mice developed an intense multiorgan inflammatory response associated with allergic airway inflammation, a striking hyperimmunoglobulinemia E, eosinophilia, and dysregulated T(H)1 and T(H)2 cytokine production in the absence of overt T(H)2 skewing. Concurrent Stat6 deficiency reversed the hyperimmunoglobulinemia E and eosinophilia and delayed mortality, which is consistent with a pathogenic role for allergic inflammation in Foxp3 deficiency.

CONCLUSION

Allergic dysregulation is a common and fundamental consequence of loss of CD4(+)CD25(+) T(R) cells caused by Foxp3 deficiency in different species. Abnormalities affecting T(R) cells might contribute to a variety of allergic diseases.

The HIV-1 protein Nef enhances viral pathogenicity and accelerates disease progression in vivo. Nef potentiates T cell activation by an unknown mechanism, probably by optimizing the intracellular environment for HIV replication. Using a new T cell reporter system, we have found that Nef more than doubles the number of cells expressing the transcription factors NF-kappaB and NFAT after TCR stimulation. This Nef-induced priming of TCR signaling pathways occurred independently of calcium signaling and involved a very proximal step before protein kinase C activation. Engagement of the TCR by MHC-bound Ag triggers the formation of the immunological synapse by recruiting detergent-resistant membrane microdomains, termed lipid rafts. Approximately 5-10% of the total cellular pool of Nef is localized within lipid rafts. Using confocal and real-time microscopy, we found that Nef in lipid rafts was recruited into the immunological synapse within minutes after Ab engagement of the TCR/CD3 and CD28 receptors. This recruitment was dependent on the N-terminal domain of Nef encompassing its myristoylation. Nef did not increase the number of cell surface lipid rafts or immunological synapses. Recently, studies have shown a specific interaction of Nef with an active subpopulation of p21-activated kinase-2 found only in the lipid rafts. Thus, the corecruitment of Nef and key cellular partners (e.g., activated p21-activated kinase-2) into the immunological synapse may underlie the increased frequency of cells expressing transcriptionally active forms of NF-kappaB and NFAT and the resultant changes in T cell activation.

Increasing resistance to chloroquine necessitates the evaluation of other antimalarial therapies in Africa. We compared the efficacies of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and AQ + SP for the treatment of uncomplicated falciparum malaria in a randomized trial of patients 6 months of age or older in Bobo-Dioulasso, Burkina Faso. Of the 944 patients enrolled, 829 (88%; 53% under 5 years of age) were assigned 28-day efficacy outcomes. For all regimens, early treatment failures were uncommon (< 2%). Considering all treatment failures based on WHO criteria, AQ + SP was most efficacious (failures in 4.2%), followed by SP (9.1%) and AQ (17.9%; P < 0.02 for all pairwise comparisons). Considering only clinical failures, relative efficacies were similar (failures in 2.1% with AQ + SP, 6.5% with SP, and 13.2% with AQ; P < 0.02 for all pairwise comparisons). The risk of recrudescence was lower with AQ + SP (2.1%) compared with SP (6.1%, P = 0.02) and AQ (8.1%, P = 0.001). Risks of new infection were lower with AQ + SP (2.1%) and SP (2.4%) compared with AQ (9.1%, P < 0.001 for both comparisons). No serious adverse events were seen. AQ + SP appears to offer a highly effective, inexpensive, and available therapy for the treatment of uncomplicated malaria in Burkina Faso.