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Objective: Identify predictors of non-compliance with first round screening exams in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial., Method: The PLCO was conducted from 1993 to 2011 at 10 US institutions. A total of 154,897 healthy men and women ages 55-74 years were randomized. Intervention arm participants were invited to receive gender-appropriate screening exams for prostate, lung, colorectal and ovarian cancer. Using intervention-arm data (73,036 participants), non-compliance percentages for 13 covariates were calculated, as were unadjusted and adjusted odds ratios (ORs), and 95% confidence intervals. Covariates included demographic factors as well as factors specific to PLCO (e.g., method of consent, distance from screening center)., Results: The rate of non-compliance was 11% overall but varied by screening center. Significant associations were observed for most covariates but indicated modest increases or decreases in odds. An exception was the use of a two-step consent process (consented intervention arm participants for exams after randomization) relative to a one-step process (consented all participants prior to randomization) (OR: 2.2, 95% CI: 2.0-2.5). Non-compliance percentages increased with further distance from screening centers, but ORs were not significantly different from 1., Conclusions: Many factors modestly influenced compliance. Consent process was the strongest predictor of compliance., (Published by Elsevier Inc.)

Background: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial provides us an opportunity to describe interval lung cancers not detected by screening chest X-ray (CXR) compared to screen-detected cancers., Methods: Participants were screened for lung cancer with CXR at baseline and annually for two (never smokers) or three (ever smokers) more years. Screen-detected cancers were those with a positive CXR and diagnosed within 12 months. Putative interval cancers were those with a negative CXR screen but with a diagnosis of lung cancer within 12 months. Potential interval cancers were re-reviewed to determine whether lung cancer was missed and probably present during the initial interpretation or whether the lesion was a "true interval" cancer., Results: 77,445 participants were randomized to the intervention arm with 70,633 screened. Of 5227 positive screens from any screening round, 299 resulted in screen-detected lung cancers; 151 had potential interval cancers with 127 CXR available for re-review. Cancer was probably present in 45/127 (35.4%) at time of screening; 82 (64.6%) were "true interval" cancers. Compared to screen-detected cancers, true interval cancers were more common among males, persons with <12 years education and those with a history of smoking. True interval lung cancers were more often small cell, 28.1% vs. 7.4%, and less often adenocarcinoma, 25.6% vs. 56.2% (p<0.001), more advanced stage IV (30.5% vs. 16.6%, p<0.02), and less likely to be in the right upper lobe, 17.1% vs. 36.1% (p<0.02)., Conclusion: True interval lung cancers differ from CXR-screen-detected cancers with regard to demographic variables, stage, cell type and location. ClinicalTrials.gov number: NCT00002540., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Hispanics are underrepresented in medical research. At the National Lung Screening Trial's University of Colorado Denver screening center, traditional recruitment methods resulted in enrollment of few Hispanics. In response, the center adopted culturally sensitive recruitment techniques, including use of carefully-crafted bilingual materials. Bilingual interviewers were hired, and persons familiar with culture and language of groups of different Hispanic origin were consulted. Representation of Hispanics among participants enrolled at the Colorado center increased nearly threefold, from 3.3 to 9.4 %, after adoption of these methods. In this manuscript, we report on the specialized recruitment methods that were developed and how they were used to address known barriers to Hispanic recruitment.

The synthesis of porous hydroxyapatite scaffolds is essential for biomedical applications such as bone tissue engineering and replacement. One way to induce macroporosity, which is needed to support bone in-growth, is to use protein additives as foaming agents. Another reason to use protein additives is the potential to introduce a specific biofunctionality to the synthesized scaffolds. In this work, we study the rheological properties of a hydroxyapatite suspension system with additions of the proteins bovine serum albumin (BSA), lysozyme (LSZ) and fibrinogen (FIB). Both the rheology of the bulk phase as well as the interfacial shear rheology are studied. The bulk rheological data provides important information on the setting behavior of the thixotropic suspension, which we find to be faster with the addition of FIB and LSZ and much slower with BSA. Foam bubble stabilization mechanisms can be rationalized via interfacial shear rheology and we show that it depends on the growth of interfacial films at the suspension/air interface. These interfacial films support the stabilization of bubbles within the ceramic matrix and thereby introduce macropores. Due to the weak interaction of the protein molecules with the hydroxyapatite particles of the suspension, we find that BSA forms the most stable interfacial films, followed by FIB. LSZ strongly interacts with the hydroxyapatite particles and thus only forms thin films with very low elastic moduli. In summary, our study provides fundamental rheological insights which are essential for tailoring hydroxyapatite/protein suspensions in order to synthesize scaffolds with controlled porosities., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2)., Methods: We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods., Results: At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2., Conclusions: Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Background: Lung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer-screening programs., Methods: At 33 U.S. centers, from August 2002 through April 2004, we enrolled asymptomatic participants, 55 to 74 years of age, with a history of at least 30 pack-years of smoking. The participants were randomly assigned to undergo annual screening, with the use of either low-dose CT or chest radiography, for 3 years. Nodules or other suspicious findings were classified as positive results. This article reports findings from the initial screening examination., Results: A total of 53,439 eligible participants were randomly assigned to a study group (26,715 to low-dose CT and 26,724 to chest radiography); 26,309 participants (98.5%) and 26,035 (97.4%), respectively, underwent screening. A total of 7191 participants (27.3%) in the low-dose CT group and 2387 (9.2%) in the radiography group had a positive screening result; in the respective groups, 6369 participants (90.4%) and 2176 (92.7%) had at least one follow-up diagnostic procedure, including imaging in 5717 (81.1%) and 2010 (85.6%) and surgery in 297 (4.2%) and 121 (5.2%). Lung cancer was diagnosed in 292 participants (1.1%) in the low-dose CT group versus 190 (0.7%) in the radiography group (stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112). Sensitivity and specificity were 93.8% and 73.4% for low-dose CT and 73.5% and 91.3% for chest radiography, respectively., Conclusions: The NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography, suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that have staff experienced in chest CT. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Background/aims: Colonoscopy may be less effective in preventing cancer in the proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit differential effect on adenoma recurrence by colon subsite., Methods: We examined the association of age, sex, body mass index, smoking status and use of nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma recurrence among 1,864 participants in the Polyp Prevention Trial. We used multinomial logistic regression models to calculate the relative risk ratios (RRR) and 95% CI., Results: 733 (39.3%) participants had adenoma recurrence (228 distal only, 369 proximal only and 136 synchronous proximal and distal adenoma). When compared to participants without adenoma recurrence, no factor was associated with an increased risk of distal only adenoma recurrence. Age 65-69 years (RRR = 1.47, 95% CI 1.00-2.16), age ≥70 years (RRR = 2.24, 95% CI 1.57-3.20), and male sex (RRR = 1.73, 95% CI 1.32-2.27) were positively associated with proximal only adenoma recurrence. NSAIDs use was associated with a reduced risk of adenoma recurrence by similar magnitude in distal (RRR = 0.78, 95% CI 0.58-1.07) and proximal colon (RRR = 0.77, 95% CI 0.60-1.00)., Conclusions: We did not find any modifiable risk factor that differentially increases proximal as compared to distal adenoma recurrence to be clinically useful for targeted intervention., (Copyright © 2013 S. Karger AG, Basel.)

Background and Study Aims: Obesity is a risk factor for colorectal neoplasia. Lifestyle modifications, including weight loss, have been advocated to reduce the risk. However, no prospective study has evaluated whether weight loss actually affects adenoma recurrence. The aim of this study was to examine whether weight change (loss or gain) over 4 years is associated with adenoma recurrence., Patients and Methods: A total of 1826 patients with colorectal adenoma in the Polyp Prevention Trial had their height and weight measured at baseline. Adenoma recurrence was determined by end of trial colonoscopy 4 years after study entry when patients' weights were re-measured. Poisson regression models were used to evaluate body mass index (BMI), weight change over 4 years, and the risk of any adenoma and advanced adenoma recurrence., Results: Adenoma recurrence was observed in 723 patients (39.6%), 118 (6.5%) of whom had advanced adenoma recurrence. Among those with baseline BMI < 25 kg/m² (n = 466), BMI 25-29 kg/m² (n = 868), and BMI ≥ 30 kg/m² (n = 492), the recurrence rate was 34.5%, 41.0%, and 41.9%, respectively. Obesity was associated with an increased risk of adenoma recurrence (RR = 1.19; 95%CI 1.01-1.39) and advanced adenoma recurrence (RR = 1.62; 95%CI 1.01-2.57). However, when compared with those with relatively stable weight (weight change < 5 lb) over the 4-year trial, weight gain or loss was not associated with adenoma recurrence. This was consistent, regardless of the baseline BMI., Conclusions: Weight loss or gain over 4 years does not affect adenoma recurrence. This study does not support weight loss alone as an effective intervention for reducing adenoma recurrence., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Before evidence of efficacy, lung cancer screening was being ordered by many physicians. The National Lung Screening Trial (NLST), which showed a 20% reduction in lung cancer mortality among those randomized to receive low-dose computed tomography (LDCT), will likely lead to increased screening use., Methods: We estimated the prevalence of chest X-ray and CT use in the United States using data from the 2010 National Health Interview Survey (NHIS). Subjects included 15,537 NHIS respondents aged ≥40 years without prior diagnosis of lung cancer. Estimates of the size of the U. S. population by age and smoking status were calculated. Multivariate logistic regression examined predictors of test use adjusting for potential confounders., Results: Twenty-three percent of adults reported chest X-ray in the previous year and 2.5% reported chest X-ray specifically to check for lung cancer; corresponding numbers for chest CT were 7.5% and 1.3%. Older age, black race, male gender, smoking, respiratory disease, personal history of cancer, and having health insurance were associated with test use. Approximately, 8.7 million adults in the United States would be eligible for LDCT screening according to NLST eligibility criteria., Conclusions and Impact: Monitoring of trends in the use of lung screening tests will be vital to assess the impact of NLST and possible changes in lung cancer screening recommendations and insurance coverage in the future. Education of patients by their physicians, and of the general public, may help ensure that screening is used appropriately, in those most likely to benefit., (©2012 AACR)

Background: Many clinical trials rely on participant report to first learn about study events. It is therefore important to have current contact information and the ability to locate participants should information become outdated. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) and the Lung Screening Study (LSS) component of the National Lung Screening Trial, two large randomized cancer screening trials, enrolled almost 190,000 participants on whom annual contact was necessary. Ten screening centers participated in both trials. Centers developed methods to track participants and trace them when necessary. We describe the methods used to keep track of participants and trace them when lost, and the extent to which each method was used., Methods: Screening center coordinators were asked, using a self-administered paper questionnaire, to rate the extent to which specific tracking and tracing methods were used., Results: Many methods were used by the screening centers, including telephone calls, mail, and internet searches. The most extensively used methods involved telephoning the participant on his or her home or cell phone, or telephoning a person identified by the participant as someone who would know about the participant's whereabouts. Internet searches were used extensively as well; these included searches on names, reverse-lookup searches (on addresses or telephone numbers) and searches of the Social Security Death Index. Over time, the percentage of participants requiring tracing decreased., Conclusions: Telephone communication and internet services were useful in keeping track of PLCO and LSS participants and tracing them when contact information was no longer valid., (Published by Elsevier Inc.)

The phase transition between the cubic diamond (cd) and beta-tin (β-Sn) phases of Si under pressure and the region of interaction of the two phases are studied by first-principles total energy calculations. For a non-vibrating crystal we determine the pressure of the thermodynamic phase transition p(t) = 96 kbar, the Gibbs free energy barrier at p(t) of ΔG = 19.6 mRyd/atom that stabilizes the phases against a phase transition and the finite pressure range in which both phases are stable. We show that the phases in that pressure range are completely described by three equilibrium lines of states along which the structure, the total energy E, the hydrostatic pressure p that would stabilize the structure and the values of G all vary. Two equilibrium lines describe the two phases (denoted the ph-eq line, ph is cd or β-Sn phase); a third line is a line of saddle points of G with respect to structure (denoted the sp-eq line) that forms a barrier of larger G against instability of the metastable ranges of the phase lines. An important conclusion is that the sp-eq line merges with the two ph-eq lines: one end of the sp-eq line merges with the cd-eq line at high pressure, the other end merges with the β-Sn-eq line at low pressure. The mergers end the barrier protecting the metastable ranges of the two ph-eq lines, hence the lines go unstable beyond the mergers. The mergers thus simplify the phase diagram by providing a natural termination to the stable parts of all metastable ranges of the ph-eq lines. Although 96 kbar is lower than the experimental transition pressure, we note that phonon pressure raises the observed transition pressure.

Objectives: To report participant recruitment experiences in a large, US randomized controlled trial (RCT) of lung cancer screening, with the aim of providing information that may be of use to researchers who wish to conduct similar future studies., Setting: The National Lung Screening Trial (NLST), an RCT that demonstrated a 20% lung cancer mortality reduction with low dose helical computed tomography screening, relative to single-view chest radiograph screening. Thirty-three US medical centres recruited 53,454 participants from August 2002 through April 2004., Methods: After recruitment was completed, centre co-ordinators were asked to complete a questionnaire addressing the extent to which specific methods were used and, for each specific method, numbers enrolled and total cost of the effort. Cost per enrollee was calculated. Co-ordinators also were asked to report lessons learned., Results: Twenty-two centres returned questionnaires. Use of recruitment method varied by centre. Among centres reporting number enrolled by method, about 19,000 participants were enrolled with direct mail, about 4200 with mass media, and about 1000 with community outreach. Cost per enrollee varied across centres but medians were (US) $101 (direct mail), $79 (mass media), and $4 (community outreach). Co-ordinators reported that it was important to know where to find persons likely to be eligible and interested, and how best to approach them., Conclusions: Most NLST participants were recruited through direct mail, although median cost per participant was highest for that method.

Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the "UK Biobank," which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which "process" expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.

Purpose: Although current practice guidelines do not recommend screening asymptomatic patients for lung cancer, physicians may still order lung cancer screening tests. No recent national survey of health care professionals has focused on lung cancer screening. In this study, we examined the lung cancer screening practices of US primary care physicians and characteristics of those who order lung cancer screening tests., Methods: We conducted a nationally representative survey of practicing primary care physicians in 2006-2007. Mailed questionnaires assessed the physicians' knowledge of lung cancer screening guidelines, beliefs about the effectiveness of screening tests, and ordering of screening chest radiograph, low-dose spiral computed tomography, or sputum cytology in the past 12 months. Clinical vignettes were used to assess the physicians' intentions to screen asymptomatic 50-year-old patients with varying smoking histories for lung cancer., Results: A total of 962 family physicians, general practitioners, and general internists completed questionnaires (cooperation rate = 76.8%). Overall, 38% had ordered no lung cancer screening tests; 55% had ordered chest radiograph, 22% low-dose spiral computed tomography, and less than 5% sputum cytology. In multivariate modeling, physicians were more likely to have ordered lung cancer screening tests if they believed that expert groups recommend lung cancer screening or that screening tests are effective; if they would recommend screening for asymptomatic patients, including patients without substantial smoking exposure; and if their patients had asked them about screening., Conclusions: Primary care physicians in the United States frequently order lung cancer screening tests for asymptomatic patients, even though expert groups do not recommend it. Primary care physicians and patients need more information about lung cancer screening's evidence base, guidelines, potential harms, and costs to avert inappropriate ordering.

In October 2011, the U.S. Preventive Services Task Force (USPSTF, or "Task Force") released draft recommendations on prostate cancer screening with prostate-specific antigen (PSA), concluding that "PSA-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary." This statement was accompanied by a grade "D" recommendation, which indicates that in the Task Force's judgment there "is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits." The Task Force, an independent panel of nonfederal (U.S.) experts in prevention and evidence-based medicine, conducts systematic evidence reviews of preventive health care services and makes recommendations about preventive services in primary care. Task Force recommendations do not set U.S. federal policy but can and do influence reimbursement and clinical practice. In this article, we will present evidence the Task Force considered when making its decision, including two highly influential randomized controlled trials (RCTs) of prostate cancer screening, the European Randomized Study of Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The two trials arrived at different conclusions about the efficacy of routine prostate cancer screening, but similar conclusions about the accompaniment of clinically relevant harms with prostate cancer screening, including overdiagnosis (screen detection of cancers that never would be diagnosed in the absence of screening). We also will present other available evidence on benefits and harms of PSA-based screening and consider that evidence and the findings of ERSPC and PLCO in conjunction with one another.

Background: Randomized controlled trials (RCTs) evaluating cancer screening modalities usually employ cause-specific mortality as their primary endpoint. Because death certificate cause of death can be inaccurate, RCTs frequently use review committees to assign an underlying cause of death. We describe the National Lung Screening Trial's (NLST's) death review approach, the Endpoint Verification Process (EVP), which strives to minimize errors in assignment of cause of death due to lung cancer., Methods: Deaths selected for review include those with a notation of lung cancer on the death certificate and those occurring among participants ever diagnosed with lung cancer. Other criteria that trigger death review include, but are not limited to, death within 6 months of a screen suspicious for lung cancer and death within 60 days of certain diagnostic evaluation procedures associated with a screen suspicious for lung cancer or a lung cancer diagnosis. EVP requires concordance on whether death was due to lung cancer. Deaths are first reviewed by the EVP chair. If concordance is not achieved, the death is next reviewed by an Endpoint Verification Team (EVT) member. If concordance between the chair- and member-assigned cause of death is not achieved, the death is next reviewed by a group of at least three EVT members. Cause of death is assigned at the step in which concordance was achieved, or if necessary, at the team review., Conclusions: NLST's EVP is designed to produce a highly accurate count of lung cancer deaths., (Published by Elsevier Inc.)

Background: The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer., Methods: From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009., Results: The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02)., Conclusions: Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

Background: Colonoscopy may be less efficacious in reducing colorectal cancer mortality in the proximal compared with the distal colon. A greater likelihood for missed and recurrent adenomas in the proximal colon may contribute to this phenomenon., Objective: To examine whether a proximal adenoma is associated with the risk and location of missed and recurrent adenomas., Design: Prospective., Setting: Polyp Prevention Trial., Participants: A total of 1864 patients with an adenoma at baseline underwent a follow-up colonoscopy 4 years later (adenoma recurrence). Of these, 1731 underwent a clearing colonoscopy 1 year after the baseline examination (missed adenoma)., Main Outcome Measurements: Association of baseline adenoma location with the risk and location of adenomas found at colonoscopy performed 1 year and 4 years later., Results: At the year 1 colonoscopy, 598 patients (34.6%) had an adenoma (missed adenoma). Compared with those with a distal-only adenoma at baseline, patients with a proximal-only adenoma at baseline were more likely to have any missed adenomas (relative risk [RR] 1.28; 95% CI, 1.09-1.49) and a proximal-only missed adenoma (RR 2.05; 95% CI, 1.49-2.80). At the year 4 colonoscopy, 733 patients (39.3%) had adenoma recurrence. Patients with a baseline proximal-only adenoma were more likely to have any adenoma recurrence (RR 1.14; 95% CI, 1.00-1.31) and a proximal-only adenoma recurrence (RR 1.52; 95% CI, 1.15-2.02). Sensitivity analyses involving missed adenomas did not materially affect the risk or location of recurrent adenomas at year 4 colonoscopy., Limitation: Lesions may still be missed on repeated colonoscopies., Conclusions: Missed and recurrent adenomas are more likely to be in the proximal colon., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Application has been made of first-principles total-energy band-structure theory to find the equilibrium states under constant pressure of the super-hard cubic diamond (cd) and hexagonal diamond (hd) structures of carbon (C), boron nitride (BN) and medium-hard silicon (Si). The absolute stability of the equilibrium state is found by determinations of the breakdown under pressure of several deformations of lattice parameters around the equilibrium state. The calculations show that the hd structures are much stronger than the cd structures. Thus the γ angle of the hd structure of both C and BN is stable for pressures greater than 20 Mbar while the γ angle of the cd structures breaks down at 13 and 11 Mbar respectively. Also the bulk moduli B of the hd structure of C and BN are substantially greater than the B values of the cd structure above 2 Mbar; the B values of hd structures of C and BN are 20% greater than cd structures at p = 20 Mbar. However the cd structures have greater stability relative to the hd structures as shown by a lower Gibbs free energy at pressures up to 20 Mbar. Comparison is made with the pressure dependences of the medium-hard crystals of Si in the same structures, which show notably different behavior.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented., (© RSNA, 2010)

We assessed the educational impact of a primetime network TV storyline that addressed cancer patient navigators. An online survey was administered after the episode aired. Exposed respondents saw the episode (n = 336); unexposed respondents did not (n = 211). Exposed respondents were more likely to report they would recommend a patient navigator (61% vs. 48%, p = 0.01). Clips of the episode were shown to raise awareness of patient navigators in a Congressional Committee meeting before the Patient Navigator Act was signed into law (2005). Entertainment education can have a positive impact on cancer knowledge and can contribute to policy-level decisions.

Background: The National Lung Screening Trial (NLST), a randomized study conducted at 33 US sites, is comparing lung cancer mortality among persons screened with reduced dose helical computerized tomography and among persons screened with chest radiograph. In this article, we present characteristics of the study population., Methods: Eligible participants were aged 55-74 years and were current or former smokers with a cigarette smoking history of at least 30 pack-years. Randomization was stratified by site, sex, and age. To assess representativeness of the study population, demographic characteristics of individuals from the general population who met NLST age and smoking history inclusion criteria were obtained from the Tobacco Use Supplement of the US Census Bureau Current Population Surveys., Results: The NLST enrolled 53 456 persons, with 26 733 randomly assigned to chest radiograph screening and 26 723 to computerized tomography screening. Characteristics of the participants were as follows: 31 533 (59%) were men, 39 234 (73%) were younger than 65 years, 25 779 (48%) were current smokers, and 16 839 (32%) had a college or higher degree. Median cigarette exposure was 48 pack-years. Among Tobacco Use Supplement respondents who met NLST age and smoking history criteria, 59% were men, 65% were younger than 65 years, and 57% were current smokers. Median cigarette exposure among this group was 47 pack-years, and 14% had a college degree or higher., Conclusion: The NLST cohort has a distribution of sex and pack-year history that is similar to the component of the general US population that meets the major NLST eligibility criteria; however, NLST participants are younger, better educated, and less likely to be current smokers.

Background: No high-quality study to date has shown that screening reduces lung cancer mortality, and expert groups do not recommend screening for asymptomatic individuals. Nevertheless, lung cancer screening tests are available in the U.S., and primary care physicians (PCPs) may have a role in recommending them to patients., Purpose: This study describes U.S. PCPs' beliefs about and recommendations for lung cancer screening and examines characteristics of PCPs who recommend screening., Methods: A nationally representative survey of practicing PCPs was conducted in 2006-2007. Mailed questionnaires were used to assess PCPs' beliefs about lung cancer screening guidelines and the effectiveness of screening tests and to determine whether PCPs would recommend screening for asymptomatic patients. Data were analyzed in 2009., Results: Nine hundred sixty-two PCPs completed the survey (absolute response rate=70.6%; cooperation rate=76.8%). One quarter said that major guidelines support lung cancer screening. Two thirds said that low-radiation dose spiral computed tomography (LDCT) screening is very or somewhat effective in reducing lung cancer mortality in current smokers; LDCT was perceived as more effective than chest x-ray or sputum cytology. Responding to vignettes describing asymptomatic patients of varying smoking exposure, 67% of PCPs recommended lung cancer screening for at least one of the vignettes. Most PCPs recommending screening said they would use chest x-ray; up to 26% would use LDCT. In adjusted analyses, PCPs' beliefs and practice style were strongly associated with their lung cancer screening recommendations., Conclusions: Many PCPs' lung cancer screening beliefs and recommendations are inconsistent with current evidence and guidelines. Provider education regarding the evidence base and guideline content of lung cancer screening is indicated., (Published by Elsevier Inc.)

The most rigorous and valid approach to evaluating cancer screening modalities is the randomized controlled trial (RCT). RCTs are major undertakings and the intricacies of trial design, operations, and management are generally underappreciated by the typical researcher. The purpose of this article is to inform the reader of the "nuts and bolts" of designing and conducting cancer screening RCTs. Following a brief introduction as to why RCTs are critical in evaluating screening modalities, we discuss design considerations, including the choice of design type and duration of follow-up. We next present an approach to sample-size calculations. We then discuss aspects of trial implementation, including recruitment, randomization, and data management. A discussion of commonly employed data analyses comes next, and includes methods for the primary analysis (comparison of cause-specific mortality rates between the screened and control arms for the cancer of interest), as well as for secondary endpoints such as sensitivity. We follow with a discussion of sequential monitoring and interim analysis techniques, which are used to examine the primary outcome while the trial is ongoing. We close with thoughts on lessons learned from past cancer screening RCTs and provide recommendations for future trials. Throughout the presentation we illustrate topics with examples from completed or ongoing RCTs, including the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the National Lung Screening Trial (NLST)., (Published by Elsevier Inc.)

Background: It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility., Methods: A total of 60, 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race., Results: Among 57 561 whites and 3011 blacks who underwent FSG, 13,743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas <10 mm), or colorectal cancer., Conclusions: We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in colorectal cancer racial disparity than biology.

Background: Often in randomized controlled trials of cancer screening, cause of death is determined by a mortality review committee. However, little is known regarding how findings from mortality review compare to those from death certificates alone., Purpose: To examine the results of four different U. S. trials of cancer screening when death certificate data only were used, as compared to results using all available mortality review information., Methods: Trials included were the Health Insurance Plan of New York breast screening trial (HIP), the Minnesota trial of fecal occult blood testing, and the Johns Hopkins and Mayo Lung Projects, which each examined chest x-ray and sputum cytology. The sensitivity, specificity, positive and negative predictive values, and Cohen's kappa for death certificates were calculated for all arms of all trials. Separate intention-to-screen analyses were conducted for each trial using cause of death information from either death certificates alone or full mortality review data., Results: Generally there was excellent agreement between the death certificates and the mortality review committee as to the underlying cause of death (kappa >0.85 in all cases); death certificate agreement was similar between arms in all trials. Modest changes in the screening effectiveness estimates were observed when mortality review information was utilized, ranging from a 9% decrease to a 2% increase in the calculated mortality rate ratios. However, in one instance (HIP) a statistically significant benefit of screening was observed when mortality review committee data were used (rate ratio (RR) 0.77, 95% confidence interval (CI) 0.62- 0.95) but not when death certificate data were used (RR 0.82, 95% CI 0.65-1.03)., Limitations: Although considered to be the gold standard, even carefully conducted mortality review may result in errors in cause of death assignment., Conclusions: For each trial, results were similar regardless of the source of cause of death information.

Unlabelled: Previous studies evaluating whether risk factors for gastric cancer are also associated with colorectal cancer (CRC) have shown inconsistent results. We prospectively examined the association of atrophic gastritis, a pre-malignant condition for gastric cancer and long-term sequelae common to many exposure factors, and the risk of incident CRC., Methods: A total of 20,928 Finnish male smokers, aged 50-69, who were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) had serum pepsinogen I (SPGI) levels measured. Participants with low SPGI levels (< 25 microg/l; n = 1,665) were invited for gastroscopy. Of these, 1,059 (63.6%) participants underwent gastroscopy and atrophic gastritis was histologically confirmed in 1,006 (95.0%) participants. We used Cox proportional hazards regression to evaluate the risk of incident CRC., Results: During a mean follow-up of 11.3 years (236,258 person-years), 425 incident CRCs were diagnosed. The incidence rates were 1.82, 1.48, and 1.82 per 1,000 person-years of follow-up for participants with normal SPGI (> or =25 microg/l), low SPGI, and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal SPGI, there was no increased risk of CRC among subjects with low SPGI (Adjusted Hazard Ratio (HR) = 0.71; 95% CI: 0.47-1.05) and among those with histologically confirmed atrophic gastritis (Adjusted HR = 0.86; 95% CI: 0.55-1.34)., Conclusion: Atrophic gastritis is not associated with an increased risk of colorectal cancer among male smokers.

Background: Pancreatic cancer is a highly fatal disease without screening tests. Studies have suggested possible etiologic similarities between gastric and pancreatic cancers. Atrophic gastritis, a pre-malignant condition for gastric cancer, is characterized by low serum pepsinogen I (SPGI) level. We hypothesized that low SPGI level may be associated with an increased risk of pancreatic cancer and be a useful biomarker for the disease., Methods: Our analytic cohort included 20,962 participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) who had SPGI level measured. Of these, 1663 (7.9%) subjects had low SPGI levels (<25 microg/l) and were invited for gastroscopy which was completed in 1059 (63.7%) participants. Atrophic gastritis was histologically confirmed in 1006 (95.0%) subjects. We used Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer., Results: During follow-up of up to 16.3 years (mean=10.8 years; 226,325 person-years), 227 incident pancreatic cancers were diagnosed. The incidence rates were 9.9, 11.3, and 12.7 per 10,000 person-years of follow-up for participants with normal pepsinogen level (> or = 25 microg/l), low pepsinogen level and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal pepsinogen levels, there was no statistically significant increased risk of pancreatic cancer among subjects with low pepsinogen level (adjusted HR=1.01; 95% CI: 0.63-1.62) or those with histologically confirmed atrophic gastritis (adjusted HR=1.13; 95% CI: 0.66-1.95)., Conclusions: Atrophic gastritis, serological or histological, is not associated with increased risk of pancreatic cancer. These findings do not provide any evidence for potential usefulness of SPGI for pancreatic cancer screening.

Background: : Two randomized controlled trials of lung cancer screening initiated in the 1970s, the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study, compared 1 arm that received annual chest X-ray and 4-monthly sputum cytology (dual-screen) to a second arm that received annual chest X-ray only. Previous publications from these trials reported similar lung cancer mortality between the 2 groups. However, these findings were based on incomplete follow-up, and each trial on its own was underpowered to detect a modest mortality benefit., Methods: : The authors estimated the efficacy of lung cancer screening with sputum cytology in an intention-to-screen analysis of lung cancer mortality, using combined data from these trials (n = 20,426)., Results: : Over (1/2) of squamous cell lung cancers diagnosed in the dual-screen group were identified by cytology; these cancers tended to be more localized than squamous cancers diagnosed in the X-ray only arm. After 9 years of follow-up, lung cancer mortality was slightly lower in the dual-screen than in the X-ray only arm (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.05). Reductions were seen for squamous cell cancer deaths (RR, 0.79; 95% CI, 0.54-1.14) and in the heaviest smokers (RR, 0.81; 95% CI, 0.67-1.00). There were also fewer deaths from large cell carcinoma in the dual-screen group, although the reason for this is unclear., Conclusions: : These data are suggestive of a modest benefit of sputum cytology screening, although we cannot rule out chance as an explanation for these findings. Cancer 2009. (c) 2009 American Cancer Society.

Structures and properties of many of the phases of Ca under pressure are calculated from first principles by a systematic procedure that minimizes total energy E with respect to structure under the constraint of constant volume V. The minima of E are followed on successive sweeps of lattice parameters for 11 of 14 Bravais symmetries for one-atom-per-cell structures. The structures include the four orthorhombic phases. Also included are the hexagonal close-packed and cubic diamond phases with two atoms per primitive cell. No uniquely orthorhombic phases are found; all one-atom orthorhombic phases over a mega-bar pressure range are identical to higher-symmetry phases. The simple cubic phase is shown to be stable where it is the ground state. The number of distinct one-atom phases reduces to five plus the two two-atom phases. For each of these phases the Gibbs free energy at pressure p, G(p), is calculated for a non-vibrating lattice; the functions G(p) give the ground state at each p, the relative stabilities of all phases and the thermodynamic phase transition pressures for all phase transitions over a several-megabar range.

Background and Aims: Prospective information on the use and yield of surveillance colonoscopy is limited. We examined the use and yield of surveillance colonoscopy among participants in the Polyp Prevention Trial (PPT) after the 4-year dietary intervention trial ended., Methods: We followed a cohort of 1297 participants. We calculated the cumulative probability of posttrial colonoscopy and investigated the yield and predictive factors for adenoma and advanced adenoma recurrence over a mean time of 5.9 years., Results: Seven-hundred seventy-four subjects (59.7%) had a repeat colonoscopy. Among 431 subjects with low-risk adenomas (1-2 nonadvanced adenomas) at baseline and no adenoma recurrence at the end of the PPT (lowest-risk category), 30.3% underwent a repeat colonoscopy within 4 years. Among 55 subjects who had high-risk adenomas (advanced adenoma and/or > or =3 nonadvanced adenomas) at baseline and again at the final PPT colonoscopy (highest-risk category), 41.3% had a colonoscopy within 3 years and 63.5% had an examination within 5 years. The cumulative yield of advanced adenoma through 6 years was 3.6% for the lowest-risk category, 38.9% for the highest-risk category, and ranged from 6.6% to 13.8% for intermediate-risk categories. An advanced adenoma at the final PPT colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance (hazard ratio, 6.2; 95% confidence interval, 2.5-15.4)., Conclusions: Surveillance colonoscopy was overused for low-risk subjects and underused for high-risk subjects. Advanced adenoma yield corresponded with the adenoma risk category. Resource consumption can be better managed by aligning use with the risk of adenoma recurrence.

A crystal phase in equilibrium under changing pressure traces out a line in structure space where each point corresponds to a structure. Along that equilibrium line the structure and all static properties describe the static behavior of the phase, including two sets of elastic constants and the bulk modulus. We discuss and illustrate the calculation of the equilibrium line and the properties from both the Gibbs free energy and the internal energy. We show that the bulk modulus, which gives a stress to strain ratio along the equilibrium line, has a universal relation independent of pressure to that set of elastic constants which control the stability, but not to the set of elastic constants appearing in the stress-strain relations at constant pressure.

The elastic behavior and stability of elemental crystals are studied in the neighborhood of a stable equilibrium state, also called a phase, at finite pressure p. It is shown that two kinds of elastic constants are needed to describe elasticity under pressure. One set, designated as c(ij),i,j = 1-6, determines stability or lack of it; another set, designated as c(ij)(p), describes the linear relation between small additional stresses and strains added to the crystal in equilibrium at p. The stress-strain coefficients c(ij)(p) differ from previous formulations of the stress-strain relations by Barron and Klein (1965 Proc. Phys. Soc. 85 523) and Wallace (1972 Thermodynamics of Crystals (New York: Wiley)), who give c(ij) as stress-strain coefficients. Hence we were led to verify the use of the c(ij)(p) using a first-principles numerical calculation example for face centered cubic Al at 1500 kbar. The Gibbs free energy G of the crystal under pressure is shown to provide both a simple definition of equilibrium and an efficient way to calculate all the elastic constants of a general crystal. A computer program finds stable phases by making jumps in structure from an arbitrary initial structure; the jumps converge to minima of G with respect to the structure. In the calculation, 21 elastic constants are evaluated from a special set of G values and the 6 × 6 elastic constant matrix is tested for stability.

Background: Multidisciplinary attempts to understand the etiology of breast cancer are expanding to increasingly include new potential markers of disease risk. Those efforts may have maximal scientific and practical influence if new findings are placed in context of the well-understood lifestyle and reproductive risk factors or existing risk prediction models for breast cancer. We therefore evaluated known risk factors for breast cancer in a cancer screening trial that does not have breast cancer as a study endpoint but is large enough to provide numerous analytic opportunities for breast cancer., Methods: We evaluated risk factors for breast cancer (N = 2085) among 70,575 women who were randomized in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Using Poisson regression, we calculated adjusted relative risks [RRs, with 95% confidence intervals (CIs)] for lifestyle and reproductive factors during an average of 5 years of follow-up from date of randomization., Results: As expected, increasing age, nulliparity, positive family history of breast cancer, and use of menopausal hormone therapy were positively associated with breast cancer. Later age at menarche (16 years or older vs. < 12: RR = 0.81, 95% CI, 0.65-1.02) or menopause (55 years or older vs. < 45: RR = 1.29, 95% CI, 1.03-1.62) were less strongly associated with breast cancer than was expected. There were weak positive associations between taller height and heavier weight, and only severe obesity [body mass index (BMI; kg/m(2)) 35 or more vs. 18.5-24.9: RR = 1.21, 95% CI, 1.02-1.43] was statistically significantly associated with breast cancer., Conclusion: The ongoing PLCO trial offers continued opportunities for new breast cancer investigations, but these analyses suggest that the associations between breast cancer and age at menarche, age at menopause, and obesity might be changing as the underlying demographics of these factors change., Clinical Trials Registration: (http://www.clinicaltrials.gov), NCT00002540.

To assess the accuracy of death certificates in assigning lung cancer as the underlying cause of death, death certificate data were compared to mortality review committee-determined causes of death among participants in the Mayo Lung Project. Further, the impact of death certificate misclassification on lung cancer mortality rates and Cox proportional hazards models was evaluated. The Mayo Lung Project (1971-1983) was a randomized controlled trial of lung cancer screening; participants were male smokers aged 45 years and older who were seen as outpatients at the Mayo Clinic in Rochester, Minnesota. Overall there were 237 lung cancer deaths according to mortality review, and 224 according to the death certificate (sensitivity 88.6 percent, 95 percent confidence interval (CI) 83.9, 92.4; specificity 99.1 percent, 95 percent CI 98.6, 99.5). As compared to the mortality review committee's determination, the use of death certificate data resulted only in slight decreases to the calculated lung cancer mortality rates for each screening arm, and did not result in appreciable changes to hazard ratios for lung cancer mortality in Cox regression models. In these data, death certificates were sufficiently sensitive and specific such that their use did not result in a meaningful change to mortality-based outcomes.

Background and Aims: Recent studies have suggested that some hyperplastic polyps may be associated with an increased risk of colorectal cancer. Prospective information on the risk of adenoma recurrence associated with hyperplastic polyps is limited. We sought to investigate whether the coexistence of hyperplastic polyps with adenomas increases the risk of adenoma recurrence., Methods: We used unconditional logistic regression models to examine the association between baseline hyperplastic polyps and subsequent adenoma recurrence during a 3-year follow-up evaluation, among 1637 participants in the Polyp Prevention Trial., Results: A total of 437 participants (26.7%) had hyperplastic polyps coexisting with adenomas at baseline. Of these, 132 (30.2%) had at least one hyperplastic polyp in the proximal colon, whereas 305 (69.8%) had only distal hyperplastic polyps. When compared with subjects without any hyperplastic polyps at baseline, there was no statistically significant association between the presence of baseline hyperplastic polyps and recurrence of any adenoma (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.94-1.51) or advanced adenoma (OR, 1.25; 95% CI, 0.78-2.03). Also, there was no association between hyperplastic polyp location and adenoma recurrence (OR, 1.01; 95% CI, 0.69-1.48) for any proximal hyperplastic polyp (OR, 1.26; 95% CI, 0.96-1.65) and for distal hyperplastic polyps., Conclusions: The coexistence of hyperplastic polyps with adenomas, irrespective of location, does not confer an increased risk of adenoma recurrence beyond that of adenomas alone within 3 years of follow-up evaluation. Prospective long-term studies on adenoma recurrence risk associated with hyperplastic polyps in screening populations are needed.

Objective: Electronic medical records (EMRs) have not developed much beyond the days of typewritten journals when it comes to facilitating extraction of data for quality assurance (QA) and improvement of health-care performance., Material and Methods: Based on 5 years' experience from the Norwegian Gastronet QA programme, we have developed a highly QA-profiled EMR for colonoscopy. We used a three-tier solution (client, server and database) written in the Java programming language using a number of open-source libraries. QA principles from the Norwegian paper-based Gastronet QA programme formed the basis for development of the ColoReg software. ColoReg is developed primarily for colonoscopy reporting in a screening trial, but may be used in routine clinical work. The QA module in ColoReg is well suited for intervention towards suboptimal performance in both settings., Results: We have developed user-friendly software dominated by clickable boxes and curtain menus reducing free text to a minimum. The software gives warnings when illogical registrations are entered and reasons have to be given for divergence from software recommendations for work-up and surveillance. At any time, defined performance quality parameters are readily accessible in tabular form with the named, logged-in endoscopist being compared with all other anonymized endoscopists in the database., Conclusion: The ColoReg software is developed for use in an international, multicentre trial on colonoscopy screening. It is user-friendly and secures continuous QA of the endoscopist's performance. The principles used are applicable to development of EMRs in general.

The existence and stability under pressure of three phases of vanadium are calculated from first principles. The phases are one body-centered cubic (bcc) and two rhombohedral phases (rh(u) and rh(l)), which have greater and lower α values than the primitive bcc rhombohedral cell. The bcc phase is shown in two ways to become unstable at 0.65 Mbar, in agreement with an observed phase transition, but in disagreement with previous higher estimates. The rh phases exist when the bcc phase is unstable, but the bcc phase stabilizes again at 3 Mbar, and the rh phases disappear. At 1.15 Mbar the rh(u) phase becomes and remains unstable and the rh(l) phase becomes the ground state up to 3 Mbar, where the rh(l) phase disappears and the bcc phase takes over. The theory gives four phase transitions among the phases over the pressure range from 0 to 3 Mbar; two of them are bcc to rh(u)-a low pressure (0.3 Mbar) thermodynamic transition found from Gibbs free energies being equal (not observed) and a higher pressure (0.65 Mbar) instability transition when the bcc phase becomes unstable (observed).

Objective: Recruitment of healthy subjects to long-term randomized controlled trials (RCTs) of cancer prevention or early detection has proven to be a difficult task. To quantify recruitment yield as well as characteristics of successfully recruited participants, we examined recruitment outcomes at 1 of the 10 centers participating in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, a National Cancer Institute-funded RCT of cancer screening modalities., Materials and Methods: During the early recruitment phase of PLCO (1993-1997), data on recruitment outcome were collected at the Henry Ford Health System (HFHS) in Detroit, Michigan. In this phase, HFHS identified potential participants using patient databases. Records were used to assess recruitment success by age, sex, race, household income (using area-based U.S. Census data), and preexisting morbidity. Logistic regression was used to assess whether enrollment success differed significantly according to these factors., Results: Of 74,139 persons ages 55 to 74 invited by HFHS to participate, 8,250 (11%) ;enrolled. In multivariate analyses, the odds of enrolling were modestly but significantly higher for women, Caucasians, persons in their 60's, and persons living in census blocks with higher median household income. Persons with two or more preexisting morbidities had significantly lower odds of enrolling compared to those with one or no preexisting morbidities., Conclusions: These data suggest that only a small fraction of persons invited to enroll in long-term RCTs of cancer screening modalities actually do so. In this urban, Midwestern setting, certain characteristics including age, race, and income influenced recruitment success, albeit modestly.

Background: Lack of confidence in postpolypectomy surveillance guidelines may be a factor in the observed low adherence rates among providers., Objective: To assess the 2006 postpolypectomy colonoscopy surveillance guidelines, which recommend 3-year follow-up colonoscopy for individuals with high-risk adenomas (defined as > or =3 adenomas or any advanced adenomas) and 5- to 10-year follow-up for patients with 2 or fewer nonadvanced adenomas, who are considered to be at low risk., Design: Analysis of prospective data from the Polyp Prevention Trial., Setting: United States., Participants: 1905 patients who had colorectal adenomas removed at baseline screening or diagnostic colonoscopy and completed the trial., Measurements: Baseline adenoma characteristics, risk-stratified according to definitions used in the guidelines, were examined as predictors for advanced adenoma recurrence., Results: 125 patients (6.6%) had advanced and 629 (33.0%) had nonadvanced adenoma recurrence; 1151 (60.4%) had no recurrence within 4 years of follow-up. The probability of advanced adenoma recurrence was 0.09 (95% CI, 0.07 to 0.11) among patients with high-risk adenomas at baseline and 0.05 (CI, 0.04 to 0.06) among those with low-risk adenomas at baseline. The relative risk for advanced adenoma recurrence for patients with high-risk adenomas versus those with low-risk adenomas at baseline was 1.68 (CI, 1.19 to 2.38) when advanced adenoma recurrence was compared with no advanced adenoma recurrence and 1.76 (CI, 1.26 to 2.46) when advanced adenoma recurrence was compared with no adenoma recurrence. The c-statistics for these 2 comparisons were 0.68 and 0.72, respectively., Limitation: Participants were self-selected and had restrictions on the degree of obesity., Conclusion: Although the risk for recurrence of advanced adenoma within 4 years is greater for patients with high-risk adenomas at baseline than for those with low-risk adenomas, the discrimination of this risk stratification scheme is relatively low.

Background: Minority populations in the United States, especially blacks and Hispanics, are generally underrepresented among participants in clinical trials. Here, we report the experience of enrolling ethnic minorities in a large cancer screening trial., Methods: The Prostate, Colorectal, Lung and Ovarian (PLCO) Cancer Screening Trial is a multicenter randomized trial designed to evaluate the effectiveness of screening for the PLCO cancers. Subjects were recruited at 10 U.S. centers between 1993 and 2001. One screening center had a major special recruitment effort for blacks and another center had a major special recruitment effort for Hispanics., Results: Among almost 155,000 subjects enrolled in PLCO, minority enrollment was as follows: black (5.0%), Hispanic (1.8%) and Asian (3.6%). This compares to an age-eligible population in the combined catchment areas of the PLCO centers that was 14.0% black, 2.9% Hispanic and 5.4% Asian, and an age-eligible population across the U.S. that was 9.5% black, 6.5% Hispanic and 3.0% Asian. About half (45%) of Hispanics were recruited at the center with the special Hispanic recruitment effort. Seventy percent of blacks were recruited at two centers; the one with the major special recruitment effort and a center in Detroit whose catchment area was 20% black among age-eligibles. Blacks, Hispanics and (non-Hispanic) whites were all more highly educated, less likely to currently smoke and more likely to get regular exercise than their counterparts in the general population., Conclusion: Significant efforts were made to recruit racial/ ethnic minorities into PLCO, and these efforts resulted in enrollment levels that were comparable to those seen in many recent cancer screening or prevention trials. Blacks and Hispanics were nonetheless underrepresented in PLCO compared to their levels among age-eligibles in the overall U.S. population or in the aggregate PLCO catchment areas.

Background: A troubling aspect of cancer screening is the potential for overdiagnosis, i.e., detection of disease that, in the absence of screening, would never have been diagnosed. Overdiagnosis is of particular concern in lung cancer screening because newer screening modalities can identify small nodules of unknown clinical significance. Previously published analyses of data from the Mayo Lung Project, a large randomized controlled trial conducted among 9211 male cigarette smokers in the 1970s and early 1980s indicated that overdiagnosis might exist in lung cancer screening. At the end of follow-up (July 1, 1983), no difference in lung cancer mortality was observed, but an excess of 46 cases in the intervention arm suggested overdiagnosis. Because that excess could instead have resulted from short follow-up time, we investigated this possibility by conducting long-term lung cancer incidence follow-up., Methods: We investigated the lung cancer status through 1999 of the 7118 participants in the Mayo Lung Project who were alive and without diagnosed lung cancer in 1983 by use of medical records, surveys mailed to participants or next-of-kin, and state death certificates., Results: Information was available for 6101 participants, including 811 with inconclusive lung cancer status. From November 1971 through December 31, 1999, 585 participants in the intervention arm and 500 in the usual-care arm were diagnosed with lung cancer., Conclusions: The persistence of excess cases in the intervention arm after 16 additional years of follow-up provides continued support for overdiagnosis in lung cancer screening.

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was initiated in 1992 to examine cause-specific mortality reduction from screening for these four cancers in men and women. We report lung cancer detection results of the baseline screening round., Methods: Of the 154,942 participants enrolled, who were aged 55-74 years with no history of PLCO cancers, 77,465 were randomly assigned to the intervention arm. Current or former smokers and never smokers in this arm received an initial single-view posterior-anterior chest radiograph., Results: In the initial screen, 5991 (8.9%, 95% confidence interval [CI] = 8.7% to 9.2%) of radiographs were suspicious for lung cancer: 8.2% (95% CI = 7.9% to 8.5%) for women and 9.6% (95% CI = 9.3% to 10.0%) for men. Rates were highest for older age groups and for smokers. Among those 5991 participants with a positive screen, 206 (3.4%, 95% CI = 3.0% to 3.9%) underwent biopsy examination, 126 (61.2%, 95% CI = 54.5% to 67.8%) of whom were diagnosed with lung cancer within 12 months of the screen (59 in women and 67 in men). The positive predictive value was 2.1% (95% CI = 1.7% to 2.5%), and 1.9 lung cancers were detected per 1000 screens. Among these cancers, 44% (95% CI = 35% to 52%) were stage I non-small-cell lung cancer. High rates of lung cancer were found in current smokers (6.3 per 1000 screens) and in former smokers who had smoked within the past 15 years (4.9 per 1000 screens). The lung cancer detection rate among never smokers was 0.4 per 1000 screens; this group accounted for 11% (95% CI = 5.6% to 16.6%) of the cancers identified., Conclusions: In the baseline screen, nearly half the cancers were stage I. Whether this experience results in a reduction in lung cancer mortality is yet to be seen.

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening.

Background: Low-radiation dose spiral computed tomography (LDCT) currently is being evaluated as a screening modality for lung carcinoma in a randomized trial. Although several diagnostic algorithms for the workup of positive LDCT screens have been proposed, to the authors' knowledge there is no widely accepted standard to date and there are few nationwide data concerning how such diagnostic workups are actually being performed outside a research protocol setting., Methods: The Lung Screening Study (LSS) was a multicenter feasibility trial that randomized 1660 subjects to undergo LDCT and an equivalent number to undergo chest X-ray. Subjects with positive screens were referred to their own health care providers for diagnostic follow-up; LSS did not specify a diagnostic algorithm. LSS collected and abstracted medical records regarding procedures employed in the diagnostic workup of positive screens., Results: Of the 522 subjects with a positive LDCT screen at baseline or at Year One, 12% underwent biopsy. Biopsy was less likely to be performed in subjects with 4-9-mm nodules (5%) than in subjects with nodules measuring 10+ mm (25%) or in subjects with no nodules but other suspicious findings (15%). Among 63% of the subjects who underwent chest CT on follow-up, the median time between screening and first follow-up chest CT was 82 days. Only a minority of subjects received diagnostic workups that were consistent with published algorithms., Conclusions: The data from the current study represent the experience of subjects followed by their health care providers in five different U.S. metropolitan areas and one rural area. As such, they provide some indication of practices in the U.S. with regard to the diagnostic workup of patients with positive spiral CT screens.