Mice with sclerostin gene deletion are resistant to the severe sublesional bone loss induced by spinal cord injury.

Bone loss after spinal cord injury (SCI) is rapid, severe, and refractory to interventions studied to date. Mice with sclerostin gene deletion are resistant to the severe sublesional bone loss induced by SCI, further indicating pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging medical problem. INTRODUCTION: The bone loss secondary to spinal cord injury (SCI) is associated with several unique pathological features, including the permanent immobilization, neurological dysfunction, and systemic hormonal alternations. It remains unclear how these complex pathophysiological changes are linked to molecular alterations that influence bone metabolism in SCI. Sclerostin is a key negative regulator of bone formation and bone mass. We hypothesized that sclerostin could function as a major mediator of bone loss following SCI. METHODS: To test this hypothesis, 10-week-old female sclerostin knockout (SOST KO) and wild type (WT) mice underwent complete spinal cord transection or laminectomy (Sham). RESULTS: At 8 weeks after SCI, substantial loss of bone mineral density was observed at the distal femur and proximal tibia in WT mice but not in SOST KO mice. By µCT, trabecular bone volume of the distal femur was markedly decreased by 64 % in WT mice after SCI. In striking contrast, there was no significant reduction of bone volume in SOST KO/SCI mice compared with SOST KO/sham. Histomorphometric analysis of trabecular bone revealed that the significant reduction in bone formation rate following SCI was observed in WT mice but not in SOST KO mice. Moreover, SCI did not alter osteoblastogenesis of marrow stromal cells in SOST KO mice. CONCLUSION: Our findings demonstrate that SOST KO mice were protected from the major sublesional bone loss that invariably follows SCI. The evidence indicates that sclerostin is an important mediator of the marked sublesional bone loss after SCI, and that pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging clinical problem.

Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius.

STUDY DESIGN: Descriptive study. OBJECTIVES: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius. SETTING: This study was conducted in Bronx, NY, USA. METHODS: Three-month-old male Wistar rats were exposed to either a sham surgery (n=10) or complete T4 spinal cord transection (n=10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated. RESULTS: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the α7 or ß1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the α7 or ß1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI. CONCLUSION: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury.

Interleukin-8 as a macrophage-derived mediator of angiogenesis.

Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.

Comprehensive health management pharmacist-delivered model: impact on healthcare utilization and costs.

OBJECTIVES: To (1) examine the impact of the Comprehensive Health Management Patient Service (CHaMPS) on unplanned hospital admissions and emergency department (ED) visits in patients with chronic conditions, (2) describe the number and type of pharmacist interventions, and (3) determine the cost savings of CHaMPS. STUDY DESIGN: Retrospective, cross-sectional design with a matched comparator group. METHODS: CHaMPS integrated pharmacists within family medicine clinics to optimize medication use among patients with chronic conditions. Outcomes were the change in unplanned hospital admissions and ED visits from baseline to 180- and 365-day postintervention periods between the CHaMPS and propensity-matched comparator groups. Descriptive, bivariate (t tests and McNemar tests), and multivariate (general linear models) statistical analyses were used. Pharmacist interventions are reported and a cost-benefit analysis was conducted. RESULTS: A total of 624 patients (312 in the CHaMPS group and 312 in the comparator group) were included. Unplanned hospital admissions decreased in the CHaMPS group and increased in the comparator group (not significant). ED visits remained stable in the CHaMPS group but increased significantly in the comparator group, resulting in a significant mean change in ED visits between the groups at the 180- and 365-day postintervention periods (P = .03 for both periods). Pharmacists provided a total of 5705 medication-related problem, education, and medication reconciliation interventions (18.3 per patient). The benefit-cost ratio ranged from 2.1:1 to 2.6:1. CONCLUSIONS: CHaMPS achieved its goals by demonstrating a positive impact on ED visits and a benefit-cost ratio greater than 1.0. The cost savings of the embedded pharmacist model are most beneficial from a payer perspective or an accountable care organization approach to healthcare.

Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis.

We have shown that human macrophages (m phi s) play an important role in the elaboration of chemotactic cytokines in rheumatoid arthritis (RA) (Koch, A. E., S. L. Kunkel, J. C. Burrows, H. L. Evanoff, G. K. Haines, R. M. Pope, and R. M. Strieter. 1991. J. Immunol. 147:2187; Koch, A. E., S. L. Kunkel, L. A. Harlow, B. Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope, and R. M. Strieter. 1992. J. Clin. Invest. 90:772; Koch, A. E., P. J. Polverini, S. L. Kunkel, L. A. Harlow, L. A. DiPietro, V. M. Elner, S. G. Elner, and R. M. Strieter. 1992. Science (Wash. DC). 258:1798). Recently, m phi inflammatory protein-1 (MIP-1 alpha), a cytokine with chemotactic activity for m phi s and neutrophils (PMNs), has been described. We have examined the production of MIP-1 alpha using sera, synovial fluid (SF), and synovial tissue (ST) from 63 arthritic patients. MIP-1 alpha was higher in RA SF (mean, 29 +/- 8 ng/ml [SE]) compared with other forms of arthritis (2.8 +/- 1.7), or osteoarthritis (0.7 +/- 0.4; P < 0.05). RA SF MIP-1 alpha was greater than that found in either RA or normal peripheral blood (PB) (P < 0.05). Anti-MIP-1 alpha neutralized 36 +/- 3% (mean +/- SE) of the chemotactic activity for m phi s, but not PMNs, found in RA SFs. RA SF and PB mononuclear cells produced antigenic MIP-1 alpha. Mononuclear cell MIP-1 alpha production was augmented with phytohemagglutinin or LPS. Isolated RA ST fibroblast production of antigenic MIP-1 alpha was augmented upon incubation of cells with LPS, and to a lesser extent with tumor necrosis factor-alpha. Isolated RA ST m phi s expressed constitutive MIP-1 alpha mRNA and antigenic MIP-1 alpha. Using ST immunohistochemistry, MIP-1 alpha+ cells from RA compared with normal were predominantly m phi s and lining cells (P < 0.05). These results suggest that MIP-1 alpha plays a role in the selective recruitment of m phi s in synovial inflammation associated with RA.

Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis.

We and others have shown that cells obtained from inflamed joints of rheumatoid arthritis (RA) patients produce interleukin-8, a potent chemotactic cytokine for neutrophils (PMNs). However, IL-8 accounted for only 40% of the chemotactic activity for PMNs found in these synovial fluids. Currently, we have examined the production of the novel PMN chemotactic cytokine, epithelial neutrophil activating peptide-78 (ENA-78), using peripheral blood, synovial fluid, and synovial tissue from 70 arthritic patients. RA ENA-78 levels were greater in RA synovial fluid (239 +/- 63 ng/ml) compared with synovial fluid from other forms of arthritis (130 +/- 118 ng/ml) or osteoarthritis (2.6 +/- 1.8 ng/ml) (P < 0.05). RA peripheral blood ENA-78 levels (70 +/- 26 ng/ml) were greater than normal peripheral blood levels (0.12 +/- 0.04 ng/ml) (P < 0.05). Anti-ENA-78 antibodies neutralized 42 +/- 9% (mean +/- SE) of the chemotactic activity for PMNs found in RA synovial fluids. Isolated RA synovial tissue fibroblasts in vitro constitutively produced significant levels of ENA-78, and this production was further augmented when stimulated with tumor necrosis factor-alpha (TNF-alpha). In addition RA and osteoarthritis synovial tissue fibroblasts as well as RA synovial tissue macrophages were found to constitutively produce ENA-78. RA synovial fluid mononuclear cells spontaneously produced ENA-78, which was augmented in the presence of lipopolysaccharide. Immunohistochemical localization of ENA-78 from the synovial tissue of patients with arthritis or normal subjects showed that the predominant cellular source of this chemokine was synovial lining cells, followed by macrophages, endothelial cells, and fibroblasts. Synovial tissue macrophages and fibroblasts were more ENA-78 immunopositive in RA than in normal synovial tissue (P < 0.05). These results, which are the first demonstration of ENA-78 in a human disease state, suggest that ENA-78 may play an important role in the recruitment of PMNs in the milieu of the inflamed joint of RA patients.

Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.

Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.05) in synovial fluid from RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to synovial fluid from osteoarthritis (OA) patients (0.92 +/- 0.08), or from patients with other arthritides (2.9 +/- 1.5). MCP-1 levels in RA sera (8.44 +/- 2.33) were significantly greater than MCP-1 in normal sera (0.16 +/- 0.06). The quantities of RA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P less than 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage of RA macrophages (50 +/- 8%) as compared to either OA macrophages (5 +/- 2) or normal macrophages (1 +/- 0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18 +/- 8%) from RA synovium were positive for immunolocalization of MCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial tissue macrophages are the dominant source of this cytokine.

Effect of C-terminal of human cytosolic thymidine kinase (TK1) on in vitro stability and enzymatic properties.

Thymidine kinase (TK1) is a key enzyme in the salvage pathway of nucleotide metabolism and catalyzes the first rate-limiting step in the synthesis of dTTP, transfer of a gamma-phosphate group from a nucleoside triphosphate to the 5'-hydroxyl group of thymidine, thus forming dTMP. TK1 is cytosolic and its activity fluctuates during cell cycle coinciding with the DNA synthesis rate and disappears during mitosis. This fluctuation is important for providing a balanced supply of dTTP for DNA replication.The cell cycle specific activity of TK1 is regulated at the transcriptional level, but posttranslational mechanisms seem to play an important role for the level of functional TK1 protein as well. Thus, the C-terminal of TK1 is known to be essential for the specific degradation of the enzyme at the G2/M phase. In this work, we have studied the effect of deletion of the C-terminal 20, 40, and 44 amino acids of TK1 on in vitro stability, oligomerization, and enzyme kinetics. We found that deletion of the C-terminal fold markedly increased the stability as well as the catalytic activity.

Improving Health of At-Risk Rural Patients project: A collaborative care model.

PURPOSE: The design elements of the Improving Health of At-Risk Rural Patients (IHARP) care model are described. SUMMARY: The IHARP project evaluated the clinical, economic, and humanistic outcomes associated with the collaborative care model relative to usual care in the community. The care model was initiated in 22 level 3- certified patient-centered medical homes. The primary outcomes are the absolute change in all relevant clinical and laboratory values of patients with hypertension, hyperlipidemia, and diabetes within and between the intervention and comparator groups; the change in the absolute number of emergency department visits and hospitalizations; and the change in the cost of care among the Medicare and Medicaid intervention patients. The lessons learned during the implementation and conduction of this project over the past three years are also presented. Patient enrollment ended in December 2014, final patient care visits were concluded in the fall of 2015, and results are expected in late 2016 or early 2017. CONCLUSION: This project will provide information from patients, physicians, and midlevel providers regarding their perceptions of clinical pharmacists as collaborative care team members. Data on health outcomes, health services utilization, and costs of care drawn from over 1600 Medicare beneficiaries will provide a robust assessment of the value of the IHARP care delivery model.

Peritoneal fluid and serum autoantibody levels in patients with endometriosis.

Patients with endometriosis demonstrate autoantibody abnormalities in their peripheral blood. Whether such abnormalities can also be detected in the peritoneal cavity, has not been established. We therefore investigated autoantibodies to 6 phospholipid antigens, 5 histones and histone subfractions and 4 polynucleotides in 14 laparoscopically diagnosed endometriosis and 9 control patients, undergoing laparoscopic tubal occlusion, in both serum and peritoneal fluid. Endometriosis patients demonstrated significantly lower total immunoglobulin G (IgG) levels in peritoneal fluid than controls. In contrast, specific IgG autoantibody levels were higher in peritoneal fluids of endometriosis patients. Mean antiphospholipids and antihistones autoantibodies reached significance when serum/peritoneal fluid ratios were compared with controls. Significant differences between endometriosis and control patients were restricted to IgG isotypes and were not observed for either IgM or IgA isotypes. These data suggest an abnormal concentration of IgG antiphospholipids and antihistones antibodies within the peritoneal cavity of endometriosis patients, which may play a contributing role in the peritoneal pathology of this condition.

Danazol but not gonadotropin-releasing hormone agonists suppresses autoantibodies in endometriosis.

The effect of treatment with danazol (n = 10) or gonadotropin-releasing hormone agonists (GnRH-a) (n = 10) on autoantibody (AA) production (IgG, IgM and, IgA to 6 phospholipids, 5 histones, and 4 polynucleotides) in endometriosis was evaluated blindly in a longitudinal, prospective, randomized study. Clinical improvement, ovarian suppression, and resolution of endometriosis were comparable in both groups. Approximately 50% of patients had significant AA abnormalities initially. During treatment with danazol but not GnRH-a, AA gradually decreased in concentration and in number/patient. Total immunoglobulin levels (IgG, IgM, and IgA) also decreased only in the danazol group. This study indicates that danazol, but not GnRH-a, lowers abnormal AA associated with endometriosis.

Self-perception variables that mediate AIDS-preventive behavior in college students.

Three psychological variables--self-efficacy, control and meaning, and perceived risk--were tested in a structural model predicting AIDS-preventive behavior. Results revealed a good model fit, indicating that these psychological variables did play a role in mediating AIDS-preventive behavior in college students. A multivariate analysis of variance and individual analyses of variance conducted for men and women also revealed gender differences on individual items of self-efficacy, perceived risk, and AIDS-preventive behavior. This study underscores the importance of identifying and assessing the psychological determinants of AIDS-preventive behavior.

Stages of change and decisional balance for 12 problem behaviors.

This integrative study investigated the generalization of the transtheoretical model across 12 problem behaviors. The cross-sectional comparisons involved relationships between two key constructs of the model, the stages of change and decisional balance. The behaviors studied were smoking cessation, quitting cocaine, weight control, high-fat diets, adolescent delinquent behaviors, safer sex, condom use, sunscreen use, radon gas exposure, exercise acquisition, mammography screening, and physicians' preventive practices with smokers. Clear commonalities were observed across the 12 areas, including both the internal structure of the measures and the pattern of changes in decisional balance across stages.

Life events and substance use among adolescents: mediating effects of perceived loss of control and meaninglessness in life.

Throughout history, alcohol and other drugs have been used to provide relief in times of stress and frustration. Research has confirmed this association between disruptive life change events and substance use. It was hypothesized that two psychological constructs facilitate and mediate this relation between stress and substance use. Uncontrollable stress (negative life change events) was assumed to create a sense of loss of control, which in turn engendered a decreased level of meaning in life. This meaninglessness in life, experienced as distressful and uncomfortable, is then treated or medicated with various drug substances. This theoretical sequential model was tested in two separate studies with independent samples of adolescents (one sample collected by the Rutgers University and the other collected by the University of California, Los Angeles [UCLA]) using latent variable structural models. The Rutgers sample was cross-sectional, whereas the UCLA sample provided longitudinal data. Results supported the theoretical hypothesis that Perceived Loss of Control and Meaninglessness mediate the relation between Uncontrollable Stress and Substance Use. In the Rutgers data, the association between stress and drug use was clearly accounted for by the mediating constructs; in other words, no direct path was necessary to explain the relation between stress and general drug use. However, in the UCLA data there remained a direct influence of Uncontrollable Stress on Substance Use after accounting for the significant impact of the mediating constructs. Five other competing models were tested; four were rejected empirically, and the other was accepted, although it was less theoretically based than the mediational model.

Sexual Assertiveness Scale (SAS) for women: development and validation.

Four studies were conducted to develop and validate the Sexual Assertiveness Scale (SAS), a measure of sexual assertiveness in women that consists of factors measuring initiation, refusal, and pregnancy-sexually transmitted disease prevention assertiveness. A total of 1,613 women from both university and community populations were studied. Confirmatory factor analyses demonstrated that the 3 factors remained stable across samples of university and community women. A structural model was tested in 2 samples, indicating that sexual experience, anticipated negative partner response, and self-efficacy are consistent predictors of sexual assertiveness. Sexual assertiveness was found to be somewhat related to relationship satisfaction, power, and length. The community sample was retested after 6 months and 1 year to establish test-retest reliability. The SAS provides a reliable instrument for assessing and understanding women's sexual assertiveness.

PIP: The construct of sexual assertiveness has potential for codifying the strategies women use to achieve sexual autonomy. The Sexual Assertiveness Scale (SAS) was developed to measure initiation of wanted sexual experience, refusal of unwanted sexual experience, and prevention of pregnancy and sexually transmitted diseases (STDs) with a regular partner. Four independent studies were conducted to establish the stability of the factor structure of the SAS, evaluate the set of predictors of sexual assertiveness, further assess construct validity in a population at high risk of STDs, and test reliability through two follow-ups. A total of 1613 US women from university and community populations were included in the studies. Confirmatory factor analyses indicated that Initiation, Refusal, and Pregnancy/STD Prevention remained stable across samples. Consistent predictors of sexual assertiveness were sexual experience, anticipated negative partner response, a history of sexual victimization as an adolescent or adult, and self-efficacy. Relationship satisfaction, power, and length were moderately related to sexual assertiveness. Finally, test-retest reliability was confirmed. Use of the SAS could facilitate the design of programs to help women to become more able to negotiate condom use, for example.

Childhood sexual abuse linked with adult substance use, victimization, and AIDS-risk.

College women who report childhood sexual abuse were compared with women who do not report abuse on a number of variables concerned with problems in living. Multivariate Analysis of Variance revealed that, compared with nonabused women, sexually abused women reported significantly more negative attitudes about sexuality, less sexual assertiveness about birth control or refusing unwanted sex, less efficacy concerning HIV prevention, more anticipation of a negative response from a partner concerning safer sex, more hard-substance use, and more sexual victimization in adulthood. These results support and extend previous work in this area and argue for greater attention to relational issues for interventions with sexually abused women. Limitations to the study and future directions for research are discussed.

Commercial IgG immunoglobulin preparations exhibit IgG and IgA autoantibody reactivity at pharmacologic but not at physiologic concentrations.

IgG immunoglobulin preparations have been increasingly utilized to treat a variety of diseases. Since disease response to this form of therapy in patients with abnormal autoimmune function is often evaluated through the subsequent investigation of autoantibody levels, it is possible that autoantibody positivities reflect autoantibody reactivity of circulating immunoglobulin preparations and not of the patient's inherent B-cell activity. We therefore investigated three commercially available IgG immunoglobulin preparations separately for IgG, IgM and IgA autoantibody reactivity to six phospholipid antigens, total histone and four histone subfractions, and four polynucleotides. Universally, all three preparations demonstrated considerable IgG antiphospholipid and antihistone reactivity at dilutions of up to 1:10(3) but not antipolynucleotide reactivity. Although no IgM reactivity was detected in any of the preparations, in all three preparations surprising IgA reactivity, especially with antihistone specificity, was detected. No autoantibody reactivity was detected at dilutions compatible with physiologic conditions in vivo. Identical observations were made for lupus anticoagulant reactivity, which was evaluated by activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition (TTI). Since autoantibody reactivities and prolonged APTT assays are observed only at pharmacologic dilution levels, it is unlikely that the administration of IgG immunoglobulin preparation will affect the evaluation of autoantibody levels in patients undergoing such treatment.

The correlation between lupus anticoagulant and autoantibodies.

The presence of a positive lupus anticoagulant (LA) has recently been associated with reproductive failure. LA positivity and reproductive failure have also been associated with autoantibody abnormalities, especially antiphospholipid autoantibodies. Because the correlation between LA and autoantibody positivity has remained controversial, we retroactively investigated 326 sera of patients with reproductive failure for correlation between lupus anticoagulant and 15 autoantibodies separately for IgG, IgM, and IgA isotypes. LA by TTI and APTT correlated significantly (p less than 0.0001). Among 18 antiphospholipid isotypes, 6 (33%) correlated significantly with TTI, 5 (28%) with APTT, and 3 (17%) both with TTI and APTT. Among 15 isotypes to histone subfractions, 4 (27%) correlated significantly to TTI, 3 (20%) to APTT, and 2 (13%) to both LA assay methods. Of 12 isotypes to antipolynucleotide antibodies, 2 (17%) correlated significantly to TTI, 1 (8%) to APTT, and none to both assay methods. The correlation between LA and autoantibodies was less striking among LA-positive than LA-negative sera. LA by both TTI and APTT was primarily found to correlate with IgG and IgA autoantibodies. This occurs in decreasing frequency to phospholipids, histones, and polynucleotides. At abnormal levels of LA (by either method) the correlation with autoantibody levels is less pronounced and appears closer with IgM autoantibodies to histones and polynucleotides than antibodies to phospholipids. We conclude that the correlation between LA and autoantibodies, especially antiphospholipid antibodies, is less pronounced than often reported in the literature. Patients suspected to suffer from reproductive failure due to abnormal autoimmunity have to be screened not only with LA and/or selected antiphospholipid autoantibodies, but with a more comprehensive autoantibody profile.

Longitudinal changes in stages of change for condom use in women.

PURPOSE: This study identifies how women naturally progress through the Transtheoretical Model stages of condom use over a 1 year period, using the longitudinal dynamic methodology of latent transition analysis (LTA). DESIGN: As part of a larger study of human immunodeficiency virus risk in women, participants were assessed for their stage of condom use two times, 1 year apart. SUBJECTS: A total of 491 women who completed both assessments of the study were included in this analysis. MEASURES: Stage of condom use was assessed using two questions, which placed women into one of five stages of change for condom use (alpha = .90). RESULTS: Latent transition analysis identified the best-fitting model of naturalistic stage progression, which included both forward and backward movement. Precontemplation and maintenance were found to be the most stable stages (more than 50% of the participants remaining in that stage 1 year later), and the action stage was the least stable (15% remaining in this stage). Transition probabilities for all stages showed a high rate of relapse in the sample. CONCLUSIONS: A high proportion of women will remain within their stage of condom use over a 1-year period if no intervention is introduced. Interventions that are aimed at increasing condom use in women need to incorporate relapse prevention. In addition, the transition probabilities for the stages will help establish reasonable rates of change for intervention programs.