Differences in characteristics of men with localised prostate cancer who demonstrate low, intermediate or high prostate-specific antigen velocity.

BACKGROUND: Current diagnostic tools are inadequate for reliable prediction of prostate cancer (PCa) aggressiveness in patients with localised disease. This results in many patients being exposed to potentially unnecessary invasive treatment and its associated morbidities. In order to develop appropriate treatment strategies, it is essential to understand the differences between patients who will develop aggressive disease and those who will not. METHODS: A longitudinal study was conducted in men with localised PCa on active surveillance for their disease in which 140 subjects were followed every 3 months for up to 5 years. Change in prostate-specific antigen (PSA) over time (PSA velocity) was used as a marker for PCa progression. Subjects were categorised as slow, intermediate and fast progressors based on tertiles of PSA velocity. Differences in baseline markers were investigated using logistic regressions. Two approaches were used, slow progressors were compared with fast progressors (model 1) and slow progressors were compared with combination of intermediate and fast progressors (model 2). RESULTS: Aspirin was negatively associated with high PSA velocity in model 1 (odds ratio (95% confidence interval): 0.24 (0.06, 0.94), P-value = 0.04) and model 2 (odds ratio = 0.22 (0.08, 0.59), P-value = 0.003), whereas smoking was positively associated with high PSA velocity in model 1 (1.03 (0.92, 1.13), P-value = 0.01). CONCLUSIONS: These findings highlight the role of aspirin and smoking in PCa progression. They have potential towards risk stratification as well as PCa prevention and hence need to be investigated further.

Rate of change in central corneal thickness: a viability indicator for conventional drainage tissues in organ culture.

Organ culture of human anterior segments is a powerful tool for understanding trabecular meshwork biology. However, data from a significant percentage of cultured anterior segments are unusable because tissues fail to meet quality control requirements, such as having adequate trabecular meshwork histology. The purpose of the present study was to evaluate a novel, real time method for assessing the viability of conventional drainage tissues in the human anterior segment perfusion model. Twenty-two human anterior segments were perfusion cultured using standard techniques for one week while measuring outflow facility and central corneal thickness (CCT). After perfusion-fixation, toludine blue-stained histological sections of drainage tissues from all four quadrants of each anterior segment were graded and endothelial cell nuclei from cornea centers were stained with 4',6-diamidino-2-phenylindole and counted. We found that most anterior segments with a stable outflow facility had a CCT that decreased over time, while anterior segments with an unstable outflow facility had CCT measurements that failed to decrease over time (P<0.01). When comparing CCT measurements to histological appearance of outflow tissues, we found that in 11/11 cases, anterior segments with an acceptable histological score had a negative CCT slope (P<0.01). Conversely in 3/4 instances, anterior segments with an unacceptable histological score had a positive CCT slope. Lastly, we observed a significant relationship between CCT measurements and corneal endothelial density (P<0.01). Thus, the simple procedure of measuring CCT during anterior segment perfusion provides a second useful measure to assess the viability of the anterior segment during the perfusion process.

Poison Control Center--based syndromic surveillance for foodborne illness.

OBJECTIVES: This retrospective study evaluated the usefulness of a poison control center (PCC) data collection system in Tucson, Arizona for early detection of foodborne disease outbreaks. METHODS: A search of a PCC database identified callers with gastrointestinal symptoms attributable to suspected foodborne illnesses whose calls were received during January 1-March 31, 2000. For each foodborne illness-related call, PCC coding was compared with a predefined diarrhea/gastroenteritis syndrome. PCC calls also were evaluated by using ZIP code, age, sex, and date of symptom onset to determine if call classifications matched any laboratory-confirmed cases reported to a county health department. RESULTS: An independent review generally agreed with the PCC's classification of calls. When calls and cases were compared, only one potential match was identified. CONCLUSION: Although confirmatory diagnostic information was not available, PCC calls were not duplicative of cases evaluated by the county health department, which suggests that they represent two independent data sets. PCC data might provide a useful addition to surveillance data reported to public health agencies for the early detection of foodborne disease outbreaks. These results will now be used to develop collaborative prospective surveillance systems.

Karyometry in the early detection and chemoprevention of intraepithelial lesions.

The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.

Karyometry detects subvisual differences in chromatin organisation state between non-recurrent and recurrent papillary urothelial neoplasms of low malignant potential.

AIM: To analyse nuclear chromatin texture in non-recurrent and recurrent papillary urothelial neoplasms of low malignant potential (PUNLMPs). MATERIALS: Ninety three karyometric features were analysed on haematoxylin and eosin stained sections from 20 PUNLMP cases: 10 from patients with a solitary PUNLMP lesion, who were disease free during at least eight years' follow up, and 10 from patients with unifocal PUNLMP, one or more recurrences being seen during follow up. RESULTS: Kruskal-Wallis analysis was used to search for features showing significant differences between recurrent and non-recurrent cases. Significance was better than p<0.005 for more than 20 features. Based on significance, six texture features were selected for discriminant analysis. Stepwise linear discriminant analysis reduced Wilk's lambda to 0.87, indicating a highly significant difference between the two multivariate data sets, but only modest ability to discriminate (70% correct case classification). A box sequential classifier was used based on data derived from discriminant analysis. The classifier took three classification steps and classified 19 of the 20 cases correctly (95% correct case classification). To determine whether significant case grouping could also be obtained based on an objective criterion, the merged data sets of non-recurrent and recurrent cases were submitted to the unsupervised learning algorithm P-index. Two clusters were formed with significant differences. The subsequent application of a Cooley/Lohnes classifier resulted in an overall correct case classification rate of 85%. CONCLUSIONS: Karyometry and multivariate analyses detect subvisual differences in chromatin organisation state between non-recurrent and recurrent PUNLMPs, thus allowing identification of lesions that do or do not recur.

Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study.

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.

Statistical analysis of randomized trials in tobacco treatment: longitudinal designs with dichotomous outcome.

This article considers two important issues in the statistical treatment of data from tobacco-treatment clinical trials: (1) data analysis strategies for longitudinal studies and (2) treatment of missing data. With respect to data analysis strategies, methods are classified as 'time-naïve' or longitudinal. Time-naïve methods include tests of proportions and logistic regression. Longitudinal methods include Generalized Estimating Equations and Generalized Linear Mixed Models. It is concluded that, despite some advantages accruing to 'time-naïve' methods, in most situations, longitudinal methods are preferable. Longitudinal methods allow direct effects of the tests of time and the interaction of treatment with time, and allow model estimates based on all available data. The discussion of missing data strategies examines problems accruing to complete-case analysis, last observation carried forward, mean substitution approaches, and coding participants with missing data as using tobacco. Distinctions between different cases of missing data are reviewed. It is concluded that optimal missing data analysis strategies include a careful description of reasons for data being missing, along with use of either pattern mixture or selection modeling. A standardized method for reporting missing data is proposed. Reference and software programs for both data analysis strategies and handling of missing data are presented.

Workplace tobacco policy: progress on a winding road.

This is a report of a pre- and post-intervention telephone survey to track changes in workplace tobacco policy in Pima County, Arizona, from 1997 to 1999. During this period, an extensive effort was made to assist workplaces to establish and enforce formal tobacco use policies. A random sample of 1134 workplaces, stratified by workforce size, was surveyed in 1997. Complete interviews were conducted with 934 (82.4%) workplaces. All 934 workplaces were contacted for the follow-up survey that was conducted in 1999. Of these, 824 (88.2%) completed follow-up surveys. The analyses presented were conducted on businesses that were included in both the baseline and follow-up surveys, and that reported having at least one employee on-site (n = 813). Tobacco policies and smoke-free policies were more likely to be found in larger businesses and businesses with a predominantly female workforce. There was no clear policy progression from having no policy, to having a policy, to becoming smoke-free. There was a small but significant overall decrease (4.8%) in the proportion of businesses having policies in the last two years. We found that 10.3% (75) of businesses that had policies in 1997 had dropped their policies by 1999, and that 13.4% (73) of worksites that were smoke-free in 1997 retained tobacco policies but were not smoke-free in 1999. However, formalization of policy in writing and the number of enforcement strategies utilized increased. These findings suggest that efforts to encourage businesses to establish workplace tobacco policies must be sustained even after policies have been established.

Addressing social and cultural disparities in tobacco use.

Disparities in smoking as a function of ethnicity exist, but part of that disparity appears to be mediated by education level. Smoking prevalence differences by ethnicity disappear or decrease substantially when controlling for education level. Nonetheless, ethnicity remains an important consideration when striving to understand the mechanisms associated with smoking, as well as in the development of smoking prevention and treatment programs. In this paper, the complex interrelationships among ethnicity, social class, and smoking are discussed in brief, and a framework for developing a systematic means of addressing social disparities in tobacco use is described.

Tobacco cessation skills certification in Arizona: application of a state wide, community based model for diffusion of evidence based practice guidelines.

OBJECTIVE: To describe the development and preliminary results from a community based certification model for training in tobacco cessation skills in Arizona. DESIGN: A programme evaluation using both quantitative pre-post measures and qualitative methods. SETTING: Arizona's comprehensive tobacco control programme of state funded, community based local projects and their community partners providing tobacco treatment services for geographically, socioeconomically, and ethnically diverse communities. INTERVENTION: A three tiered model of skills based training emphasising Agency for Health Care Policy and Research guidelines, and utilising a training of trainers approach to build community capacity. Certification roles addressed basic tobacco cessation skills, tobacco cessation specialist, and tobacco treatment services manager. PARTICIPANTS: Initial target audience was community based local project personnel and their community partners, with later adoption by community organisations unaffiliated with local projects, and the general public. MAIN EVALUATION MEASURES: Process measures: participant satisfaction, knowledge, skills, and self-efficacy. OUTCOME: participant demographics, community organisations represented, post-training, cessation related activities. RESULTS: During the model's implementation year, 1075 participants attended certification training, 947 participants received basic skills certificates and 82 received specialist certificates. Pre, post, and three month measures of self efficacy showed significant and durable increases. Analysis of participant characteristics demonstrated broad community representation. At post-training follow up, 80.9% of basic skills trainees had performed at least one brief intervention and 74.8% had made a referral to intensive services. Among cessation specialists, 48.8% were delivering intensive services and 69.5% were teaching basic skills classes. CONCLUSIONS: Initial experience with Arizona's state wide, community based model for certification of tobacco cessation skills training suggests this model may be a promising method for broad, population based diffusion of evidence based tobacco cessation guidelines.