Impact of patient and navigator race and language concordance on care after cancer screening abnormalities.

BACKGROUND: Patient navigation improves the timely diagnosis of cancer among minorities, but little is known about the effects of patient and navigator race and language concordance on health outcomes. METHODS: The authors investigated the effects of patient and navigator race and language concordance on the time to diagnosis of cancer screening abnormalities among participants in the Boston Patient Navigation Research Program, a clinical effectiveness trial for women who had breast or cervical cancer screening abnormalities identified from January 1, 2007 to December 31, 2008. Hazard ratios and 95% confidence intervals were estimated using proportional hazards regression adjusting for clinical and demographic factors. RESULTS: In total, 1257 women had breast cancer screening abnormalities (n = 655) or cervical cancer screening abnormalities (n = 602) identified, and 56% were nonwhite. Language concordance was associated with timelier resolution for all patients in the cervical cancer screening abnormalities group during the first 90 days (adjusted hazard ratio, 1.46; 95% confidence interval, 1.18-1.80), and specifically for Spanish speakers during the first 90 days (adjusted hazard ratio, 1.43; 95% confidence interval, 1.10-1.84), but no difference was observed after 90 days for women who had cervical cancer screening abnormalities or at any time for those who had breast cancer screening abnormalities. Race concordance was associated with significant decreases in the time to diagnosis for minority women with breast and cervical cancer screening abnormalities in analyses stratified by race, but no differences were observed in analyses that included all women. CONCLUSIONS: Patient navigator race and language concordance improved the timeliness of care in a minority population. Patient navigators who are racially/ethnically diverse and multilingual may help address barriers to care and improve cancer outcomes for low-income minorities.

Public health, medicine, and dentistry as partners in community health: a pioneering initiative in interprofessional, practice-based education.

CONTEXT: As public health challenges grow more complex, the call for professional education to be interprofessional, collaborative, and grounded in real world practice has intensified. OBJECTIVE: In this article, we describe the development, implementation, and results of one pioneering course at Boston University that aims to prepare public health, medical, and dental students for their combined roles in community health settings. SETTING AND PARTICIPANTS: The Schools of Public Health, Medicine, and Dental Medicine jointly offered the course in partnership with 3 community organizations. Participants include MPH, MD, and DMD candidates. INTERVENTION: The course design integrates the use of "The Challenge Model" (created by Management Sciences for Health) with training in public health consultation techniques (eg, community-based participatory research, logic models, monitoring and evaluation). Teams of 6 to 8 medical and public health students collaborate with managers and staff of a community health center to address 1 organizational challenge and recommend a sustainability plan. RESULTS: Postcourse evaluations revealed that a cross-disciplinary, practice-based education model is feasible and can meet students' learning objectives and exceed expectations of community partners. We overcame formidable obstacles related to the "silo'ed" nature of academic institutions and the competing priorities within overburdened community organizations. We found that sustained project implementation was attained at some but not all sites, yet all sites highly valued the perspective and contribution of student teams. CONCLUSION: Dynamic and replicable, this practice-based education model is adaptable to professional schools whose work intersects in the real world and calls for collaborative leadership.

Lymphocytes, neuropeptides, and genes involved in alopecia areata.

Many lessons in autoimmunity - particularly relating to the role of immune privilege and the interplay between genetics and neuroimmunology - can be learned from the study of alopecia areata, the most common cause of inflammation-induced hair loss. Alopecia areata is now understood to represent an organ-restricted, T cell-mediated autoimmune disease of hair follicles. Disease induction is associated with collapse of hair follicle immune privilege in both humans and in animal models. Here, the role of HLA associations, other immunogenetic factors, and neuroendocrine parameters in alopecia areata pathogenesis are reviewed. This instructive and clinically significant model disease deserves more widespread interest in the immunology community.

Alopecia areata: a tissue specific autoimmune disease of the hair follicle.

The goal of this review is to introduce the immunologic community to alopecia areata as a model system for the study of tissue directed autoimmune disease. Alopecia areata is marked by autoimmune assault on the hair follicle resulting in hair loss. It is linked to HLA-DQ3 and evidence suggests it is mediated by T-lymphocytes with a TH1 cytokine profile. Hair follicles are an immune protected site with deficient MHC expression. Evidence is presented suggesting that alopecia areata results from loss of immune privilege with presentation of autoantigens. Alopecia areata is one of the most common human autoimmune conditions, with a lifetime risk of approximately 1.7%. Study of alopecia areata in humans is facilitated by the accessibility of scalp for biopsy. It is possible to transfer the condition with lesional human lymphocytes in a human scalp graft/SCID mouse model. There are also spontaneous animal models which share the features of the human condition. For these reasons, alopecia areata is a powerful model for study of the induction and pathogenesis of tissue directed autoimmune disease.

Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes: induction of psoriasis by cells with natural killer receptors.

This study was performed to ask whether psoriasis is a unique pathologic response of epidermis of psoriatic patients, or cells with natural killer receptors can induce psoriatic changes in skin from nonpsoriatic donors. Human nonlesional skin from five psoriatics, as well as from seven nonpsoriatics was grafted on to beige-SCID mice. Lymphocyte lines with natural killer activity, and mixed natural killer, natural killer T cell phenotype, were generated by culture of peripheral blood mononuclear cells from both psoriatic, and normal donors, in 100 U interleukin-2 per ml for 14 d. Natural killer cells were injected into the human skin grafts, and the grafts were harvested after 4 wk. Injection of natural killer cells from psoriatic donors into autologous nonlesional psoriatic skin resulted in classic psoriasis histology with a significant increase in epidermal thickness, and proliferation, as well as expression of epidermal human leukocyte antigen DR, intercellular adhesion molecule-1, CD1d, and K-16. Superantigen stimulation was not necessary. In contrast, injection of natural killer cells from normal donors into autologous normal skin did not induce the histology of psoriasis, but that of psoriasiform dermatitis. This is a nonspecific reaction pattern. These grafts also exhibited a significant increase in epidermal thickness, and proliferation. Differences from psoriasis included mild epidermal edema (spongiosis), hypergranulosis, irregular elongation of rete ridges, and lack of thinning of the suprapapillary plate. Injection of allogeneic natural killer cells into grafts also resulted in psoriasiform dermatitis, regardless of the source of natural killer cells, or skin. Psoriasis induction by cells with natural killer receptors appears to be dependent upon the source of skin. This suggests that psoriasis results from a cutaneous defect that is triggered by an autoimmune activation.

Aging of human epidermis: reversal of aging changes correlates with reversal of keratinocyte fas expression and apoptosis.

The goal of this study was to determine the role of Fas-mediated apoptosis in human epidermal aging. Epidermal Fas expression and apoptosis are increased in aged human skin. Aging changes of human epidermis, including decreased epidermal thickness and proliferation, are reversed following grafting of human skin to SCID (severe combined immunodeficiency) mice. Skin from aged participants (n = 14; mean 70.7 years), and young participants (n = 14; mean 23.4 years) was grafted to beige SCID mice, and epidermal thickness, proliferation (Ki-67 expression), apoptosis (TUNEL [Tdt-mediated dUTP nick end labeling] reaction below granular layer), and expression of Fas and FasL were determined by histology and immunochemical staining. Aged skin was associated with thinning of the epidermis, decreased epidermal proliferation, a significant increase in apoptosis below the granular layer, and epidermal Fas expression. Engraftment significantly reversed these aging changes, including apoptosis, and Fas expression. Correlation of reversal of aging changes, with decreased epidermal Fas expression and apoptosis, supports a role for Fas-mediated apoptosis in aging of human epidermis.

Mediation of alopecia areata by cooperation between CD4+ and CD8+ T lymphocytes: transfer to human scalp explants on Prkdc(scid) mice.

OBJECTIVE: To determine the role of CD4+ and CD8+ T lymphocytes in the pathogenesis of alopecia areata. DESIGN: Relapse of alopecia areata was induced in autologous human scalp grafts on Prkdc(scid) mice by injection of activated T lymphocytes derived from lesional skin. CD4+ and CD8+ T cells were separated by magnetic beads before injection. SETTING: University-based dermatology practice. PARTICIPANTS: Eleven patients with either alopecia totalis or severe alopecia areata. MAIN OUTCOME MEASURES: Hair regrowth, hair loss, and immunohistochemical findings of scalp explants. INTERVENTION: Transfer of scalp T cells to autologous lesional scalp explants on Prkdc(scid) mice. RESULTS: Injection of unseparated T cells and mixed CD4+ plus CD8+ T cells resulted in significant hair loss (P<.01) in 5 of 5 experiments. However, injection of purified CD4+ or CD8+ T cells alone did not result in reproducible hair loss. CD4+ and CD8+ T cells induced follicular expression of intercellular adhesion molecule 1 (CD54), HLA-DR, and HLA-A, HLA-B, and HLA-C after injection into scalp grafts. CONCLUSIONS: CD4+ and CD8+ T cells have a role in the pathogenesis of alopecia areata. It is hypothesized that CD8+ T cells act as the effector cells, with CD4+ T cell help. It is now necessary to look for HLA-A, HLA-B, and HLA-C associations with alopecia areata. Therapeutic manipulations that interfere with CD8+ activity should be examined.

The impact of health insurance reform on insurance instability.

We investigated the impact of the 2006 Massachusetts health care reform on insurance coverage and stability among minority and underserved women. We examined 36 months of insurance claims among 1,946 women who had abnormal cancer screening at six community health centers pre-(2004-2005) and post-(2007-2008) insurance reform. We examined frequency of switches in insurance coverage as measures of longitudinal insurance instability. On the date of their abnormal cancer screening test, 36% of subjects were publicly insured and 31% were uninsured. Post-reform, the percent ever uninsured declined from 39% to 29% (p .001) and those consistently uninsured declined from 23% to 16%. To assess if insurance instability changed between the pre- and post-reform periods, we conducted Poisson regression models, adjusted for patient demographics and length of time in care. These revealed no significant differences from the pre- to post-reform period in annual rates of insurance switches, incident rate ratio 0.98 (95%- CI 0.88-1.09). Our analysis is limited by changes in the populations in the pre- and post-reform period and inability to capture care outside of the health system network. Insurance reform increased stability as measured by decreasing uninsured rates without increasing insurance switches.

The impact of insurance coverage during insurance reform on diagnostic resolution of cancer screening abnormalities.

We examined the impact of Massachusetts insurance reform on the care of women at six community health centers with abnormal breast and cervical cancer screening to investigate whether stability of insurance coverage was associated with more timely diagnostic resolution. We conducted Cox proportional hazards models to predict time from cancer screening to diagnostic resolution, examining the impact of 1) insurance status at time of screening abnormality, 2) number of insurance switches over a three-year period, and 3) insurance history over a three-year period. We identified 1,165 women with breast and 781 with cervical cancer screening abnormalities. In the breast cohort, Medicaid insurance at baseline, continuous public insurance, and losing insurance predicted delayed resolution. We did not find these effects in the cervical cohort. These data provide evidence that stability of health insurance coverage with insurance reform nationally may improve timely care after abnormal cancer screening in historically underserved women.

Impact of depression on the intensity of patient navigation for women with abnormal cancer screenings.

Patient navigation is increasingly being used to support vulnerable patients to receive timely and quality medical care. We sought to understand whether patients with depression utilize additional patient navigation services after abnormal cancer screening. We compared depressed and non-depressed women using three different measures of intensity of patient navigation: number of patient-navigator encounters, encounter time, and number of unique barriers to care. The study population consisted of 1,455 women who received navigation after abnormal screening for breast or cervical cancer at one of six community health centers in Boston. Navigators spent a median of 60-75 minutes over one or two encounters per participant, with 49% of participants having one or more documented barrier to care. Depressed women did not differ in total numbers of encounters, encounter time, or unique barriers compared with non-depressed women. Our findings suggest that pre-existing depression does not predict which women will utilize additional navigation services.

Connecting Boston's public housing developments to community health centers: who's ready for change?

BACKGROUND: Despite close proximity to community health centers, public housing residents are at increased risk of uncontrolled chronic disease, in part because of underutilization of routine health care. OBJECTIVES: To assist in program planning, the Partners in Health and Housing Prevention Research Center (PHH-PRC) used the Community Readiness Model to compare readiness of public housing developments and community health centers to address community-identified health priorities. The model assumes that program success to affect change depends on matching the community's level of readiness to address the issue. METHODS: Key respondent interviews were conducted across 15 communities: Eight housing developments and seven health centers. Interviews were scored across six dimensions on an anchored, 9-point scale and averaged to provide a composite readiness score. Higher scores indicate increasing levels of readiness. Interview transcripts were reviewed for consistent themes. RESULTS: Health centers scored significantly higher (mean, 5.88) than housing developments (mean, 3.33), corresponding with the Preparation stage of readiness compared with the Vague Awareness stage, respectively. Both scored highest in Existing Programs and Resources and lowest in Knowledge of Efforts. Qualitative analysis revealed a lack of existing partnerships between housing developments and health centers as well as significant social barriers preventing housing residents from engaging in care. CONCLUSION: We found a mismatch in readiness to address community health priorities. Although health centers have programs to address health issues, community awareness of programs is limited and barriers to engaging in care persist. The model provided a useful tool for engaging communities into shared program planning.

Boston Patient Navigation Research Program: the impact of navigation on time to diagnostic resolution after abnormal cancer screening.

BACKGROUND: There is a need for controlled studies to assess the impact of patient navigation in vulnerable cancer populations. METHODS: Boston Patient Navigation Research Program conducted a quasi-experimental patient navigation intervention across six federally qualified inner-city community health centers, three assigned to a breast cancer navigation intervention and three assigned to a cervical cancer navigation intervention; each group then served as the control for the other. Eligible women had an abnormal breast or cervical cancer screening test conducted at one of the participating health centers during a baseline (2004-2005) or intervention period (2007-2008). Kaplan-Meier survival curves and proportional hazards regression examined the effect of patient navigation on time to definitive diagnosis, adjusting for covariates, clustering by clinic and differences between the baseline and intervention period. RESULTS: We enrolled 997 subjects in the baseline period and 3,041 subjects during the intervention period, of whom 1,497 were in the navigated arm, and 1,544 in the control arm. There was a significant decrease in time to diagnosis for subjects in the navigated group compared with controls among those with a cervical screening abnormality [aHR 1.46; 95% confidence interval (CI), 1.1-1.9]; and among those with a breast cancer screening abnormality that resolved after 60 days (aHR 1.40; 95% CI, 1.1-1.9), with no differences before 60 days. CONCLUSIONS: This study documents a benefit of patient navigation on time to diagnosis among a racially/ethnically diverse inner city population. IMPACT: Patient navigation may address cancer health disparities by reducing time to diagnosis following an abnormal cancer-screening event.

Predictors of timely follow-up after abnormal cancer screening among women seeking care at urban community health centers.

BACKGROUND: We sought to measure time and identify predictors of timely follow-up among a cohort of racially/ethnically diverse inner city women with breast and cervical cancer screening abnormalities. METHODS: Eligible women had an abnormality detected on a mammogram or Papanicolaou (Pap) test between January 2004 and December 2005 in 1 of 6 community health centers in Boston, Massachusetts. Retrospective chart review allowed us to measure time to diagnostic resolution. We used Cox proportional hazards models to develop predictive models for timely resolution (defined as definitive diagnostic services completed within 180 days from index abnormality). RESULTS: Among 523 women with mammography abnormalities and 474 women with Pap test abnormalities, >90% achieved diagnostic resolution within 12 months. Median time to resolution was longer for Pap test than for mammography abnormalities (85 vs 27 days). Site of care, rather than any sociodemographic characteristic of individuals, including race/ethnicity, was the only significant predictor of timely follow-up for both mammogram and Pap test abnormalities. CONCLUSIONS: Site-specific community-based interventions may be the most effective interventions to reduce cancer health disparities when addressing the needs of underserved populations.

Clues from alopecia areata on the role of neuropeptides in the initiation of autoimmunity.

A fascinating question regarding the pathogenesis of alopecia areata is the potential linkage with the brain. Siebenharr et al. demonstrate that substance P fibers are increased in early lesions, and that substance P treatment induces catagen follicles along with activated CD8+ T cells. Potentially, neuropeptides serve as the initial insult resulting in loss of tolerance and autoimmune disease.

Fas pulls the trigger on psoriasis.

Fas/FasL signaling is best known for induction of apoptosis. However, there is an alternate pathway of Fas signaling that induces inflammatory cytokines, particularly tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. This pathway is prominent in cells that express high levels of anti-apoptotic molecules such as Bcl-xL. Because TNF-alpha is central to the pathogenesis of psoriasis and psoriatic epidermis has a low apoptotic index with high expression of Bcl-xL, we hypothesized that inflammatory Fas signaling mediates induction of psoriasis by activated lymphocytes. Noninvolved skin from psoriasis patients was grafted to beige-severe combined immunodeficiency mice, and psoriasis was induced by injection of FasL-positive autologous natural killer cells that were activated by IL-2. Induction of psoriasis was inhibited by injection of a blocking anti-Fas (ZB4) or anti-FasL (4A5) antibody on days 3 and 10 after natural killer cell injection. Anti-Fas monoclonal antibody significantly reduced cell proliferation (Ki-67) and epidermal thickness, with inhibition of epidermal expression of TNF-alpha, IL-15, HLA-DR, and ICAM-1. Fas/FasL signaling is an essential early event in the induction of psoriasis by activated lymphocytes and is necessary for induction of key inflammatory cytokines including TNF-alpha and IL-15.

Minocycline inhibits antigen processing for presentation to human T cells: additive inhibition with chloroquine at therapeutic concentrations.

The ability of minocycline to inhibit processing of tetanus toxoid (TT) for presentation to human T cells was tested. Peripheral blood antigen presenting cells (APC) were incubated with TT before or after addition of test compounds for 4 h. APC were then fixed with paraformaldehyde, and added to autologous TT-responsive T cell lines for a proliferation assay. Minocycline (0.1-0.4 mM) gave significant inhibition of T cell response to TT and was equivalent to chloroquine. Inhibition was not observed when TT was incubated with APC before minocycline, indicating that presentation of preprocessed antigen was not inhibited. Minocycline, doxycycline, and tetracycline all inhibited the proliferation of PBMC to TT. The combination of minocycline and chloroquine resulted in additive inhibition at clinically relevant levels of both drugs (3.7 microM). This study suggests a novel immunosuppressive mechanism for minocycline, as well as possible additive anti-inflammatory effect when combined with chloroquine or hydroxychloroquine.

Alopecia areata: autoimmunity--the evidence is compelling.

There is strong evidence indicating that alopecia areata is a tissue-specific, autoimmune disease. Hair loss is associated with a perifollicular lymphocytic infiltrate made up primarily of CD4+ cells, along with a CD8+ intrafollicular infiltrate. Evidence of immune activation includes expression of HLA-DR; HLA-A,B,C; and ICAM-1 on the follicular epithelium. It is likely that the follicular expression of HLA-DR and ICAM-1 is induced by interferon-gamma produced by T cells. Antibodies to follicular epithelium are often present, but their significance is not known. Lesional scalp from alopecia areata patients grafted onto nude mice regrows hair coincident with a loss of infiltrating lymphocytes from the graft. Hair loss can be transferred to human scalp explants on SCID mice by injection of lesional T cells. It is necessary to activate the T cells by culture with follicular autoantigens. Melanocyte-associated antigens are also capable of activating T cells to induce hair loss, suggesting that they are capable of functioning as autoantigens for alopecia areata. Parallel evidence in rodent models of spontaneous alopecia areata also strongly supports a role for T cells in the pathogenesis of this condition.

Immune-mediated loss of transgene expression in skin: implications for cutaneous gene therapy.

A clearer understanding of the immune-mediated loss of transgene from cutaneous epithelium is necessary for development of effective clinical gene therapy protocols for patients who carry null mutations in the target gene. We have used retrovirus-mediated transfer of lacZ to mouse skin as a model to investigate the mechanism of immune-mediated transgene loss in skin. Transduction of C57Bl/6 mouse skin resulted in elicitation of both humoral and cellular immune responses. Antibody responses did not play a major role in the loss of transgene. Infiltration of the transduced skin with CD4(+) and CD8(+) cells and induction of transgene-specific cytotoxic T lymphocytes implied a role for T-cell-mediated responses. Transduction of mice deficient in either major histocompatibility complex (MHC) class I or class II molecules resulted in transient transgene expression. Only in MHC(-/-) mice lacking expression of both class I and class II MHC molecules was persistent transgene expression seen. These data indicate a primary role for T-cell-mediated responses in the immune-mediated loss of transgene expression. Furthermore, CD4 and CD8 T cells have overlapping roles and either population can effectively eliminate transduced cells. Therefore, long-term cutaneous gene therapy may require development of strategies to interfere with activation or function of both T cell populations.