Transition of a clinical trial into translational research: the prostate cancer prevention trial experience.

Large clinical trials provide a tremendous opportunity to integrate correlative, comprehensive biological studies with invaluable repositories of biospecimens and clinical and other data from the trial. The Prostate Cancer Prevention Trial (PCPT) was a phase III randomized, double-blind, placebo-controlled clinical trial of finasteride in 18,882 men. Clinical data and blood and tissue specimens were collected at baseline and throughout the study, offering an opportunity to create a program project to investigate hypotheses related to the biology underlying the PCPT findings as well as the etiology and risk of prostate cancer.

Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study.

The contribution of specific cancer therapies, comorbid medical conditions, and host factors to mortality risk after pediatric Hodgkin lymphoma (HL) is unclear. We assessed leading morbidities, overall and cause-specific mortality, and mortality risks among 2742 survivors of HL in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study of survivors diagnosed from 1970 to 1986. Excess absolute risk for leading causes of death and cumulative incidence and standardized incidence ratios of key medical morbidities were calculated.

Androgen receptor CAG repeat length and association with prostate cancer risk: results from the prostate cancer prevention trial.

Purpose: We investigated the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the AR gene and the risk of prostate cancer.

Materials And Methods: This is a nested case-control study of 1,159 cases and 1,353 controls from the Prostate Cancer Prevention Trial, a randomized, placebo controlled trial testing whether the 5α-reductase inhibitor finasteride could decrease the 7-year prevalence of prostate cancer. During the course of the trial men underwent annual digital rectal examination and prostate specific antigen measurement.

CD22 EXON 12 deletion as a pathogenic mechanism of human B-precursor leukemia.

Here, we report that primary leukemic cells from infants with newly diagnosed B-precursor leukemia express a truncated and functionally defective CD22 coreceptor protein that is unable to transmit apoptotic signals because it lacks most of the intracellular domain, including the key regulatory signal transduction elements and all of the cytoplasmic tyrosine residues. Expression of this structurally and functionally abnormal CD22 protein is associated with a very aggressive in vivo growth of patients' primary leukemia cells causing disseminated overt leukemia in SCID mice. The abnormal CD22 coreceptor is encoded by a profoundly aberrant mRNA arising from a splicing defect that causes the deletion of exon 12 (c.

Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial.

The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994-2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire.

Long-term survivors of childhood Ewing sarcoma: report from the childhood cancer survivor study.

Background: The survival of Ewing sarcoma (ES) patients has improved since the 1970s but is associated with considerable future health risks.

Methods: The study population consisted of long-term (> or =5-year) survivors of childhood ES diagnosed before age 21 from 1970 to 1986. Cause-specific mortality was evaluated in eligible survivors (n = 568), and subsequent malignant neoplasms, chronic health conditions, infertility, and health status were evaluated in the subset participating in the Childhood Cancer Survivor Study (n = 403).

Serum oxidized protein and prostate cancer risk within the Prostate Cancer Prevention Trial.

To evaluate the role of oxidative stress in prostate cancer risk, we analyzed serum levels of protein carbonyl groups in 1,808 prostate cancer cases and 1,805 controls, nested in the Prostate Cancer Prevention Trial, a randomized, placebo-controlled trial that found finasteride decreased prostate cancer risk. There were no significant differences in protein carbonyl levels in baseline samples between those later diagnosed with prostate cancer and those without at the end of study biopsy. Adjusted odds ratios and 95% confidence intervals (95% CI) for the 4th quartile of protein carbonyl level for the combined, placebo, and finasteride arms were 1.

Finasteride modifies the relation between serum C-peptide and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Hyperinsulinemia and obesity-related metabolic disturbances are common and have been associated with increased cancer risk and poor prognosis. To investigate this issue in relation to prostate cancer, we conducted a nested case-control study within the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial testing finasteride versus placebo for primary prevention of prostate cancer. Cases (n = 1,803) and controls (n = 1,797) were matched on age, PCPT treatment arm, and family history of prostate cancer; controls included all eligible non-whites.

Human papillomavirus types 16, 18, and 31 serostatus and prostate cancer risk in the Prostate Cancer Prevention Trial.

Since human papillomavirus (HPV) infection was first identified as a risk factor for cervical cancer, several seroepidemiologic and tissue-based studies have investigated HPV in relation to prostate cancer, another common genitourinary malignancy, with mixed results. To further inform this potential association, we conducted a large, prospective investigation of HPV types 16, 18, and 31 in relation to risk of prostate cancer in the Prostate Cancer Prevention Trial. Cases were a sample of men diagnosed with prostate cancer after visit 2 or on their end-of-study biopsy (n = 616).

Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies.

Background: Data on long-term intra-individual variability in high-sensitivity C-reactive protein (hsCRP) are needed to determine whether one measurement adequately reflects usual levels in prospective studies of on the etiology of cancer and other chronic diseases; when not reflective, the ability to statistically detect modest to moderate associations is reduced. The authors estimated the size of this source of variability and consequent attenuation of the relative risk (RR).

Methods: High-sensitivity C-reactive protein (hsCRP) concentration was measured using a high-sensitivity immunoturbidometric assay in sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT).

Predicting ischemic brain injury after intraoperative cardiac arrest during cardiac surgery using the BIS monitor.

Two patients in whom the bispectral index (BIS) decreased to zero following cardiac arrest during cardiothoracic surgery are described. The BIS value decreased to zero after cardiac arrest, and the value remained low for the remainder of the anesthetic despite successful cardiopulmonary resuscitation. Both patients were found to have severe brain injuries in the postoperative period.

Knowledge of hepatitis C virus screening in long-term pediatric cancer survivors: a report from the Childhood Cancer Survivor Study.

Background: Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion-acquired HCV.

Methods: To assess long-term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy from 1970 to 1986.

Results: More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing.

Care of the patient with enteral tube feeding: an evidence-based practice protocol.

Background: Care of patients with enteral feeding tubes often is based on tradition and textbook guidance rather than best evidence. Care practices can vary widely both between and within institutions, and this was the case at a northeastern military medical center that served as the site for this evidence-based protocol development and implementation project.

Objectives: The purpose of this study was to describe the development and implementation of an evidence-based clinical protocol for care of patients with enteral feeding tubes.

Effect of improving the quality of radiographic interpretation on the ability to predict pulmonary tuberculosis relapse.

Rationale And Objectives: Chest radiographic findings are important for diagnosis and management of tuberculosis. The reliability of these findings is therefore of interest. We sought to describe interobserver reliability of chest radiographic findings in pulmonary tuberculosis, and to understand how the reliability of these findings might affect the utility of radiographic findings in predicting tuberculosis relapse.

Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial.

Background: Several prospective studies suggest that use of cholesterol-lowering statin drugs is inversely associated with advanced stage and possibly high-grade prostate cancer. One study reported that men with low cholesterol had a lower risk of high-grade prostate cancer. Given these findings, we investigated the association between low serum cholesterol and prostate cancer risk in the Prostate Cancer Prevention Trial.

Are there health benefits associated with comprehensive smoke-free laws.

Introduction: In the past few years, comprehensive smoke-free laws that prohibit smoking in all workplaces have been introduced in many jurisdictions in the US, Canada, and Europe. In this paper, we review published studies to ascertain if there is any evidence of health benefits resulting from the implementation of these laws.

Methods: All papers relating to smoke-free legislation published in or after 2004 were considered for inclusion in this review.

Active smoking and second-hand-smoke exposure at home among Irish children, 1995-2007.

Objective: This study hypothesised a continual decline in current smoking prevalence over four calendar years (1995, 1998, 2002/03 and 2007) and no significant increase in second-hand-smoke (SHS) exposure levels at home after the workplace smoking ban of March 2004 (2007 versus 2002/03 survey) among Irish school children.

Methods: A modified ISAAC (International Study of Asthma and Allergies in Childhood) protocol was used. Children aged 13-14 years from randomly selected representative post-primary schools were studied: 2670 in 1995, 2273 in 1998, 2892 in 2002-2003, and 2805 in 2007.

Impact of radiation and chemotherapy on risk of dental abnormalities: a report from the Childhood Cancer Survivor Study.

Background: The current study was performed to describe frequencies and risk factors of altered oral health and odontogenesis in childhood cancer survivors.

Methods: In total, 9308 survivors who were diagnosed between 1970 and 1986 and 2951 siblings from the Childhood Cancer Survivor Study completed a survey that contained oral-dental health information. The authors analyzed treatment impact, socioeconomic data, and patient demographics on dental outcomes using univariate and multivariate logistic regression models to estimate odds ratios (ORs).

Predictors of marriage and divorce in adult survivors of childhood cancers: a report from the Childhood Cancer Survivor Study.

Background/objective: Adult survivors of childhood cancer can have altered social functioning. We sought to identify factors that predict marriage and divorce outcomes in this growing population.

Methods: This was a retrospective cohort study of 8,928 > or = 5-year adult survivors of childhood malignancy and 2,879 random sibling controls participating in the Childhood Cancer Survivor Study.

Alcohol consumption, finasteride, and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Background: Current research is inconclusive regarding the relation between alcohol consumption and prostate cancer risk. In this study, the authors examined the associations of total alcohol, type of alcoholic beverage, and drinking pattern with the risk of total, low-grade, and high-grade prostate cancer.

Methods: Data for this study came from the 2129 participants in the Prostate Cancer Prevention Trial (PCPT) who had cancer detected during the 7-year trial and 8791 men who were determined by biopsy to be free of cancer at the trial end.

Chemoprevention of prostate cancer.

Purpose: Due to the public health impact of prostate cancer including the burden of screening and treatment, there is significant public interest in the potential prevention of this disease. We review the most recent results of large scale randomized clinical trials.

Materials And Methods: We review the potential agents, their hypothesized mechanisms of action and challenges for the design of chemoprevention trials, including the 3 large scale trials SELECT (testing selenium and vitamin E), PCPT (testing finasteride) and REDUCE (testing dutasteride).

Brainlab: A Python Toolkit to Aid in the Design, Simulation, and Analysis of Spiking Neural Networks with the NeoCortical Simulator.

Neuroscience modeling experiments often involve multiple complex neural network and cell model variants, complex input stimuli and input protocols, followed by complex data analysis. Coordinating all this complexity becomes a central difficulty for the experimenter. The Python programming language, along with its extensive library packages, has emerged as a leading "glue" tool for managing all sorts of complex programmatic tasks.

A Component-Based Extension Framework for Large-Scale Parallel Simulations in NEURON.

As neuronal simulations approach larger scales with increasing levels of detail, the neurosimulator software represents only a part of a chain of tools ranging from setup, simulation, interaction with virtual environments to analysis and visualizations. Previously published approaches to abstracting simulator engines have not received wide-spread acceptance, which in part may be to the fact that they tried to address the challenge of solving the model specification problem. Here, we present an approach that uses a neurosimulator, in this case NEURON, to describe and instantiate the network model in the simulator's native model language but then replaces the main integration loop with its own.