Correlates and predictors of colorectal cancer screening among male automotive workers.

BACKGROUND: Most studies examining factors associated with colorectal cancer (CRC) screening (CRCS) are cross-sectional and thus temporal relationships cannot be determined. Furthermore, less attention has been paid to psychosocial predictors of CRCS. We examined both cross-sectional correlates of prior CRCS and predictors of prospective CRCS initiation and maintenance during The Next Step Trial, a 2-year worksite behavioral intervention to promote regular CRCS and dietary change. METHOD: The sample included 2,693 White male automotive workers at increased occupational risk for, but no history of, CRC who completed a baseline survey. Stratified analyses were conducted for three dependent variables (prior CRCS, CRCS initiation, and CRCS maintenance). We also assessed prior CRCS as a moderator in prospective analyses. Multivariable logistic regression analyses with generalized linear mixed models were used to adjust for cluster sampling. RESULTS: Except for education, cross-sectional correlates of prior CRCS including older age, family history of CRC or polyps, personal history of polyps, self-efficacy, family support, and intention were also significant prospective predictors of increased CRCS during the trial. Despite differences in the patterns of association for CRCS initiation and maintenance in stratified analyses, the only associations with prospective CRCS that were significantly moderated by prior CRCS were family history and CRCS availability. CONCLUSIONS: Correlates of prior CRCS that also were prospective predictors of CRCS may be suitable targets for intervention. Additionally, intervention messages addressing psychosocial constructs may be relevant for both CRCS initiation and maintenance. However, studies with more diverse samples are needed to replicate the results reported here.

Evaluation of a decision aid for families considering p53 genetic counseling and testing.

PURPOSE: Li-Fraumeni syndrome (LFS) is associated with p53 germline mutations, and carriers are at increased risk for multiple primary cancers. We evaluated outcomes following the administration of a video-based decision aid (DA) prior to clinical p53 genetic counseling and testing among persons who had previously participated in cancer genetics research. METHODS: Fifty-seven individuals at risk for a known p53 mutation completed baseline and post-DA measures of psychological outcomes, plus knowledge and attitudes regarding p53 genetic testing. Counseling and testing uptake also was recorded. RESULTS: At baseline, multivariate analysis showed that greater testing intention was associated with lower decisional conflict (P < 0.01). Compared with baseline data, multivariate analyses of post-DA outcomes showed that knowledge about LFS and genetic testing increased and decisional conflict related to testing decreased (P < 0.001). Mean cancer worries scores decreased among all participants (P < 0.001), and mean depression scores decreased for males (P < 0.05). Thirty-nine (68%) completed pre-test genetic counseling and 23 (40%) subsequently gave a blood sample for clinical genetic testing. CONCLUSION: This intervention was useful as an initial outreach and educational method for families considering p53 genetic testing, and may improve knowledge about LFS as well as psychological outcomes.

Psychological impact of genetic testing for hereditary nonpolyposis colorectal cancer.

PURPOSE: This study examines the impact of hereditary nonpolyposis colorectal cancer (HNPCC) genetic test results on psychological outcomes among cancer-affected and -unaffected participants up to 1 year after results disclosure. PATIENTS AND METHODS: A total of 155 persons completed study measures before HNPCC genetic testing, and at 2 weeks and 6 and 12 months after disclosure of test results. RESULTS: Mean scores on all outcome measures remained stable and within normal limits for cancer-affected participants, regardless of mutation status. Among unaffected carriers of HNPCC-predisposing mutations, mean depression, state anxiety, and cancer worries scores increased from baseline to 2 weeks postdisclosure and decreased from 2 weeks to 6 months postdisclosure. Among unaffected noncarriers, mean depression and anxiety scores did not differ, but cancer worries scores decreased during the same time period. Affected and unaffected carriers had higher mean test-specific distress scores at 2 weeks postdisclosure compared with noncarriers in their respective groups; scores decreased for affected carriers and all unaffected participants from 2 weeks to 12 months postdisclosure. Classification of participants into high- versus low-distress clusters using mean scores on baseline psychological measures predicted significantly higher or lower follow-up scores, respectively, on depression, state anxiety, quality of life, and test-specific distress measures, regardless of mutation status. CONCLUSION: Although HNPCC genetic testing does not result in long-term adverse psychological outcomes, unaffected mutation carriers may experience increased distress during the immediate postdisclosure time period. Furthermore, those with higher levels of baseline mood disturbance, lower quality of life, and lower social support may be at risk for both short- and long-term increased distress.

How families communicate about HNPCC genetic testing: findings from a qualitative study.

Little is known about how hereditary nonpolyposis colon cancer (HNPCC) genetic counseling and testing information is communicated within at-risk families. This article describes findings from a qualitative study of 39 adult members from five families with known HNPCC-predisposing mutations. We evaluated how information from HNPCC genetic counseling and testing was disseminated in these families and how family members reacted to and acted on this information. We included family members who had been diagnosed with an HNPCC syndrome cancer, unaffected individuals who were at 50% risk of carrying a mutation, and their spouses. Participants included those who had undergone testing and those who had not. In general, all families had shared the news about an HNPCC mutation with at-risk relatives. Communication about HNPCC genetic counseling and testing followed the norms used for conveying other nonurgent family news. Mutation noncarriers, nontesters, and those who were not biological relatives were less involved in discussing genetic counseling and testing and perceived these processes as less relevant to them. Although all family members were generally willing to share information about HNPCC, probands and mutation carriers informed extended family members and actively persuaded others to seek counseling or testing. Family members who were persuaded to seek those services by the proband were more likely to have counseling and testing and were more likely to seek those services sooner. Genetic counseling should attempt to identify the existing communication norms within families and ways that family members can take an active role in encouraging others to learn about their cancer risk and options for testing. Interventions may also need to emphasize the relevance of hereditary cancer information beyond the immediate family and to unaffected family members who may be central to the communication process (e.g., spouses of mutation carriers).

A social network analysis of communication about hereditary nonpolyposis colorectal cancer genetic testing and family functioning.

Hereditary cancers are relational diseases. A primary focus of research in the past has been the biological relations that exist within the families and how genes are passed along family lines. However, hereditary cancers are relational in a psychosocial sense, as well. They can impact communication relationships within a family, as well as support relationships among family members. Furthermore, the familial culture can affect an individual's participation in genetic counseling and testing endeavors. Our aims are (a) to describe the composition of familial networks, (b) to characterize the patterns of family functioning within families, (c) to analyze how these patterns relate to communications about genetic counseling and testing among family members, and (d) to identify influential family members. Specifically, we asked how the relationship between mutation status, kinship ties, and family functioning constructs, e.g., communication, cohesion, affective involvement, leadership, and conflict, was associated with discussions about genetic counseling and testing. We used social network analysis and random graph techniques to examine 783 dyadic relationships in 36 members of 5 hereditary nonpolyposis colorectal cancer (HNPCC) families interviewed from 1999-2000. Results suggest that in these five HNPCC families, two family members are more likely to discuss genetic counseling and testing if either one carries the mutation, if either one is a spouse or a first-degree relative of the other, or if the relationship is defined by positive cohesion, leadership, or lack of conflict. Furthermore, the family functioning patterns suggest that mothers tend to be the most influential persons in the family network. Results of this study suggest encouraging family members who act in the mother role to take a "team approach" with the family proband when discussing HNPCC risks and management with family members.

Intention to be screened over time for colorectal cancer in male automotive workers.

Intention is an important construct in health promotion research, yet very little is known about whether cross-sectional correlates of intention to be screened for colorectal cancer (CRC) also predict intention over time or intention change. We used survey data from The Next Step Trial, a worksite health promotion trial, to address the following questions: (1) What is the consistency over time of intention to be screened for CRC? (2) Are the patterns and magnitude of associations between intention to be screened and the Preventive Health Model variables consistent over time? (3) What are the predictors of improving weaker intention to be screened, i.e., changing to strong intention? (4) What are the predictors of no change in strong intention to be screened, i.e., maintaining strong intention? and (5) What is the predictive ability of the models to predict intention to be screened for CRC? The study population consisted of white male automotive employees who responded to baseline (1993) and follow-up (1994 and 1995) surveys and did not have CRC at baseline or develop it during the study period. Of 5042 eligible workers, 2903 (58%) returned a baseline survey, and 2556 (88% of survey responders) met eligibility criteria; 75% (1929 of 2556) returned the year 1 survey, and 74% (1892 of 2556) returned the year 2 survey. We fit logistic regression models separately for the Preventive Health Model variables measured at baseline and each outcome (intention at year 1, intention at year 2, improving weaker intention, and no change in strong intention). The prevalence of strong intention to be screened for CRC was approximately 60% on all three surveys. Overall, 66% maintained their baseline intention over time. The most consistent predictors of strong intention, improving weaker intention, and no change in strong intention were family support, belief in the salience and coherence of screening, prior screening, and lack of concern about screening-related discomfort. Intention measured at baseline predicted intention measured 1 and 2 years later. Perceived susceptibility and lack of fear and worry about a CRC diagnosis predicted improving weaker intention. Having a family history of CRC or polyps predicted maintaining strong intention. Plant factors, self-efficacy, and beliefs about polyp removal were not predictors beyond the baseline year. Basing intervention development on cross-sectional associations may miss important factors or may incorrectly assume that cross-sectional associations are stable over time. A more focused, tailored intervention may be developed using factors that consistently predict intention.

Regulation of tumor growth by IFN-gamma in cancer immunotherapy.

Tumor immunity involves a concerted interplay between cytokines and effector cells. Extensive efforts have focused on understanding the roles of cytokines and their interactions with effector cells for the production of effective tumor immunity. One cytokine that is well recognized to play a central role in coordinating tumor immune responses is IFN-gamma. IFN-gamma exerts its biological effects through interaction with an IFN-gamma receptor that is ubiquitously expressed on nearly all cells. In this review, we discuss the positive and negative effects of IFN-gamma signaling in the tumor cell on tumor growth.

IFN-gamma-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-gamma.

The importance of CD4(+) T cells in the induction of an optimal antitumor immune response has largely been attributed to their ability to provide costimulatory signals for the priming of MHC class I-restricted CD8(+) CTL. However, many reports have demonstrated a requirement for CD4(+) T cells in the effector phase of tumor rejection indicating a greater responsibility for CD4(+) T cells in controlling tumor outgrowth. We demonstrate here a critical role for CD4(+) T cells in restraining initial tumor development through the inhibition of tumor angiogenesis. Using a tumor variant that is unresponsive to IFN-gamma, we show that tumor responsiveness to IFN-gamma is necessary for IFN-gamma-dependent inhibition of tumor angiogenesis by CD4(+) T cells. These studies reveal a pivotal role for CD4(+) T cells in controlling early tumor development through inhibition of tumor angiogenesis.

IFN-gamma can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen.

Although IFN-gamma has been generally thought to enhance antitumor immune responses, we found that IFN-gamma can promote tumor escape in the CT26 colon carcinoma by down-regulating the protein expression of an endogenous tumor Ag. gp70, the env product of the endogenous ecotropic murine leukemia virus, has been reported to be the immunodominant Ag of CT26. We show that IFN-gamma down-regulates intracellular and surface levels of gp70 protein resulting in a reduced lysis by CTL, which is restored by pulsing IFN-gamma-treated CT26 with the L(d)-restricted immunodominant AH1 epitope derived from gp70. To investigate the role of CT26 sensitivity to IFN-gamma in vivo, we constructed two variants of CT26, CT26.mugR and CT26.IFN, that are unresponsive to IFN-gamma or express IFN-gamma, respectively. We demonstrate using these variants that tumor responsiveness to IFN-gamma promotes a reduction in tumor immunogenicity in vivo that is correlated with an increased tumor incidence in immune mice. Analysis of the tumors from mice challenged with CT26 or CT26.mugR revealed infiltration of CD8 T cells secreting IFN-gamma. We conclude that IFN-gamma secreted by tumor-infiltrating T cells promotes tumor escape through the down-regulation of the endogenous tumor Ag gp70. These findings have impact on the design of effective antitumor vaccine strategies.

Noncontact system-guided simplified right atrial linear lesions using radiofrequency transcatheter ablation for treatment of refractory atrial fibrillation.

This article describes our experience with a staged "hybrid" approach to the treatment of drug resistant AF, in which the completeness of a single linear lesion in the RA was verified with a noncontact mapping system. Inferior vena cava-tricuspid annulus ablation was performed and followed by the creation of a single intercaval lesion. The study population consisted of 24 patients with a 3.4 +/- 1.6-year history of drug resistant, severely symptomatic, lone paroxysmal (n = 19), or persistent (n = 5) AF. During a follow-up of 8 +/- 2.6 months, 12 (50%) patients remained asymptomatic and 6 (25%) had a significant decrease in AF episodes, while the arrhythmia was unchanged in 5 (21%) patients and aggravated in 1 (4%) patient. Overall, a favorable clinical result was achieved in 18 (75%) patients.

Mapping of atrial activation with a noncontact, multielectrode catheter in dogs.

BACKGROUND: Endocardial mapping of sustained arrhythmias has traditionally been performed with a roving diagnostic catheter. Although this approach is adequate for many tachyarrhythmias, it has limitations. The purpose of this study was to evaluate a novel noncontact mapping system for assessing atrial tachyarrhythmias. METHODS AND RESULTS: The mapping system consists of a 9F multielectrode-array balloon catheter that has 64 active electrodes and ring electrodes for emitting a locator signal. The locator signal was used to construct a 3-dimensional right atrial map; it was independently validated and was highly accurate. Virtual electrograms were calculated at 3360 endocardial sites in the right atrium. We evaluated right atrial activation by positioning the balloon catheter in the mid right atrium via a femoral venous approach. Experiments were performed on 12 normal mongrel dogs. The mean correlation coefficient between contact and virtual electrograms was 0.80+/-0.12 during sinus rhythm. Fifty episodes of atrial flutter induced in 11 animals were evaluated. In the majority of experiments, complete or almost complete reentrant circuits could be identified within the right atrium. Mean correlation coefficient between virtual and contact electrograms was 0.85+/-0.17 in atrial flutter. One hundred fifty-six episodes of pacing-induced atrial fibrillation were evaluated in 11 animals. Several distinct patterns of right atrial activation were seen, including single-activation wave fronts and multiple simultaneous-activation wave fronts. Mean correlation coefficient between virtual and contact electrograms during atrial fibrillation was 0.81+/-0.18. The accuracy of electrogram reconstruction was lower at sites >4.0 cm from the balloon center and at sites with a high spatial complexity of electrical activation. CONCLUSIONS: This novel noncontact mapping system can evaluate conduction patterns during sinus rhythm, demonstrate reentry during atrial flutter, and describe right atrial activation during atrial fibrillation. The accuracy of electrogram reconstruction was good at sites <4.0 cm from the balloon center, and thus the system has the ability to perform high-resolution multisite mapping of atrial tachyarrhythmias in vivo.

Activity of a ritonavir plus saquinavir-containing regimen in patients with virologic evidence of indinavir or ritonavir failure.

OBJECTIVE: To evaluate the virologic activity of a ritonavir plus saquinavir-containing regimen in patients who have failed an indinavir or ritonavir-containing regimen. DESIGN: Patients were identified through a retrospective study evaluating the incidence of indinavir or ritonavir failure in our clinic. PATIENTS: Eighteen patients failing indinavir or ritonavir therapy and who switched to a ritonavir-saquinavir-containing regimen were evaluated. Indinavir or ritonavir failure was defined as a plasma viral load > 1500 copies/ml (branched DNA) after 16 weeks of continuous therapy. INTERVENTIONS: All patients switched to ritonavir (400 mg twice daily) plus saquinavir (400 mg twice daily) and received concurrent therapy with two nucleoside reverse transcriptase inhibitors (NRTI). Twelve of the 18 patients modified their NRTI regimen at the time ritonavir-saquinavir was initiated. OUTCOME MEASURES: Plasma viral load was monitored using a branched DNA assay. Genotypic analysis was performed using a point mutation differential hybridization technique, and was confirmed with direct sequencing. RESULTS: Fourteen out of 18 patients completed at least 24 weeks of therapy; the remaining four patients discontinued therapy after week 12 due to a lack of virologic response or intolerance. Plasma viral load decreased a median 1.4 log10 after 4 weeks of treatment with ritonavir-saquinavir. Only four patients had a greater than 0.5 log10 decrease in viral load after 24 weeks of therapy. In eight out of 10 patients evaluated, the V82A mutation was present at the time of the switch to ritonavir-saquinavir. Viral rebound on ritonavir-saquinavir was associated with the emergence of mutations at amino acids 46, 48, 54 and 90. CONCLUSION: The combination of ritonavir, saquinavir and two NRTI resulted in a moderate but transient suppression of viral replication in patients who have failed indinavir or ritonavir therapy. Failure of ritonavir-saquinavir may be associated with the emergence of mutations associated with resistance to ritonavir/saquinavir monotherapy, particularly the L90M mutation.

Developing a hospital emergency preparedness program.

The emergency preparedness program is not a static entity that only needs to be taken off the shelf and looked at once or twice a year. The various components of the program require that it be a daily part of the hospital's routine. Only by becoming a part of the everyday operation of the hospital can the full benefits of an emergency preparedness program be realized in an actual disaster. A part of the recovery activities after a hospital experiences an actual disaster should be to examine all phases of the emergency preparedness program. The program should be viewed as if it were being designed from scratch. Time should be taken to identify any areas of weakness, develop a plan for making the necessary corrections, and then implement those corrections.