Case-control studies in evaluating prostate cancer screening: an overview

Objectives: Ongoing randomized controlled screening trials for prostate cancer have not shown a beneficial effect on prostate cancer mortality reduction yet. A large number of observational (non-randomized) studies on prostate cancer screening have been published with contradictory outcome. This paper reviews the current case-control studies. Methods: Seven case-control studies of screening for prostate cancer were identified in a PubMed search, published from 1991 onwards, all conducted in North America. The screening test was either digital rectal examination (DRE) alone or in combination with PSA. Results: One DRE case-control study, found a significant preventive effect, whereas two others showed no effect of DRE screening on prostate cancer mortality nor on the occurrence of metastatic disease. Conflicting results were also observed in the studies assessing the effect of PSA/DRE. Only one study showed a significant 27% mortality reduction in the White male cohort, but found no effects in Blacks. The most recent study showed that screening with PSA/DRE was not protective in reducing prostate cancer mortality. Conclusions: Our review of the case-control studies does not indicate a benefit of prostate cancer screening. An answer has to come from the ERSPC trial, in Europe, and the PLCO trial, in the US, of which the outcomes are expected in 2007–2010. # 2006 European Association of Urolog

Ethnicity and prostate cancer: The way to solve the screening problem?

In their analysis in BMC Medicine, Lloyd et al. provide individual patient lifetime risks of prostate cancer diagnosis and prostate cancer death stratified by ethnicity. This easy to understand information is helpful for men to decide whether to start prostate-specific antigen testing (i.e. screening). A higher lifetime risk of prostate cancer death in some ethnic groups is not automatically a license to start screening. The potential benefit in the form of reducing metastases and death should still be weighed against the potential risk of over diagnosis. In case of ethnicity, this harm-to-benefit ratio does not differ between groups. Stratifying men for screening based on ethnicity is therefore not optimal and will not solve the current screening problem. Other methods for risk-stratifying men have been proven to produce a more optimal harm-to-benefit ratio

Algorithms, nomograms and the detection of indolent prostate cancer

Purpose: Prostate cancer is the most commonly diagnosed cancer in men. However, only about 12% of the men diagnosed with prostate cancer will die of their disease. Result: The serum PSA test can detect prostate cancers early, but using a PSA based cut-off indication for prostate biopsy results in unnecessary testing in app. 75-80% of the men and perhaps even more important the serum PSA test cannot tell how aggressive the cancer is. To decrease unnecessary testing different test results are often combined, converted into a probability and displayed graphically. There are more than 40 of these so called nomograms in the case of prostate cancer. These nomograms can be divided into two categories, namely those that predict biopsy outcome using results from serum determination(s) or non-invasive tests such as the DRE and TRUS. The second category represents those nomograms that predict tumor characteristics and prognosis using information coming from pathology review. Conclusion: The ultimate nomogram able to predict tumor characteristics and progression purely based on non-invasive testing will for a large part put an end to the negative side effects and uncertainties that coincide with the early detection of prostate cancer, if it will ever be made

Rotterdam Prostate Cancer Risk Calculator: Development and Usability Testing of the Mobile Phone App

BACKGROUND: The use of prostate cancer screening tools that take into account relevant prebiopsy information (ie, risk calculators) is recommended as a way of determining the risk of cancer and the subsequent need for a prostate biopsy. This has the potential to limit prostate cancer overdiagnosis and subsequent overtreatment. mHealth apps are gaining traction in urological practice and are used by both practitioners and patients for a variety of purposes. OBJECTIVE: The impetus of the study was to design, develop, and assess a smartphone app for prostate cancer screening, based on the Rotterdam Prostate Cancer Risk Calculator (RPCRC). METHODS: The results of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) study were used to elaborate several algorithms that allowed the risk of prostate cancer to be estimated. A step-by-step workflow was established to ensure that depending on the available clinical information the most complete risk model of the RPCRC was used. The user interface was designed and then the app was developed as a native app for iOS. The usability of the app was assessed using the Post-Study System Usability Questionnaire (PSSUQ) developed by IBM, in a group of 92 participants comprising urologists, general practitioners, and medical students. RESULTS: A total of 11 questions were built into the app, and, depending on the answers, one of the different algorithms of the RPCRC could be used to predict the risk of prostate cancer and of clinically significant prostate cancer (Gleason score ≥7 and clinical stage >T2b). The system usefulness, information quality, and interface quality scores were high-92% (27.7/30), 87% (26.2/30), and 89% (13.4/15), respectively. No usability problems were identified. CONCLUSIONS: The RPCRC app is helpful in predicting the risk of prostate cancer and, even more importantly, clinically significant prostate cancer. Its algorithms have been externally validated before and the usability score shows the app's interface is well designed. Further usability testing is required in different populations to verify these results and ensure that it is easy to use, to warrant a broad appeal, and to provide better patient care.info:eu-repo/semantics/publishedVersio

Quasiparticle relaxation rate and shear viscosity of superfluid 3He-A_1 at low temperatures

Quasiparticle relaxation rate,$\tau_{p}^{-1}$, and the shear viscosity tensor of the A_1-phase of superfluid 3He are calculated at low temperatures and melting pressure, by using Boltzmann equation approach in momentum space. The collision integral is written in terms of inscattering and outscattering collision integrals. The interaction between normal and Bogoliubov quasiparticles is considered in calculating transition probabilities in the binary, decay and coalescence processes. We obtain that both $\tau_{p\uparrow}^{-1}$ and $\tau_{p\downarrow}^{-1}$ are proportional to $T^2$ >. The shear viscosities $\eta_{xy}$, $\eta_{xz}$ and $\eta_{zz}$ are proportional to $(T/T_c)^{-2}$. The constant of proportionality of the shear viscosity tensor is in nearly good agreement with the experimental results of Roobol et al., and our exact theoretical calculation.Comment: 8 pages, some typos were correcte

Shear viscosity of the A_1-phase of superfluid 3He

The scattering processes between the quasiparticles in spin- up superfluid with the quasiparticles in spin-down normal fluid are added to the other relevant scattering processes in the Boltzmann collision terms. The Boltzmann equation has been solved exactly for temperatures just below T_c_1. The shear viscosity component of the A_1- phase drops as C_1(1-T/T_c_1)^(1/2). The numerical factor C_1 is in fairly good agreement with the experiments

Prostate cancer screening in Europe and Asia

Prostate cancer (PCa) is the second most common cancer among men worldwide and even ranks first in Europe. Although Asia is known as the region with the lowest PCa incidence, it has been rising rapidly over the last 20 years mostly due to the introduction of prostate-specific antigen (PSA) testing. Randomized PCa screening studies in Europe show a mortality reduction in favor of PSA-based screening but coincide with high proportions of unnecessary biopsies, overdiagnosis and subsequent overtreatment. Conclusive data on the value of PSA-based screening and hence the balance between harms and benefits in Asia is still lacking. Because of known racial variations, Asian countries should not directly apply the European screening models. Like in the western world also in Asia, new predictive markers, tools and risk stratification strategies hold great potential to improve the early detection of PCa and to reduce the worldwide existing negative aspects of PSA-based PCa screening

Improving prediction models with new markers: A comparison of updating strategies

Background: New markers hold the promise of improving risk prediction for individual patients. We aimed to compare the performance of different strategies to extend a previously developed prediction model with a new marker. Methods: Our motivating example was the extension of a risk calculator for prostate cancer with a new marker that was available in a relatively small dataset. Performance of the strategies was also investigated in simulations. Development, marker and test sets with different sample sizes originating from the same underlying population were generated. A prediction model was fitted using logistic regression in the development set, extended using the marker set and validated in the test set. Extension strategies considered were re-estimating individual regression coefficients, updating of predictions using conditional likelihood ratios (LR) and imputation of marker values in the development set and subsequently fitting a model in the combined development and marker sets. Sample sizes considered for the development and marker set were 500 and 100, 500 and 500, and 100 and 500 patients. Discriminative ability of the extended models was quantified using the concordance statistic (c-statistic) and calibration was quantified using the calibration slope. Results: All strategies led to extended models with increased discrimination (c-statistic increase from 0.75 to 0.80 in test sets). Strategies estimating a large number of parameters (re-estimation of all coefficients and updating using conditional LR) led to overfitting (calibration slope below 1). Parsimonious methods, limiting the number of coefficients to be re-estimated, or applying shrinkage after model revision, limited the amount of overfitting. Combining the development and marker set using imputation of missing marker values approach led to consistently good performing models in all scenarios. Similar results were observed in the motivating example. Conclusion: When the sample with the new marker information is small, parsimonious methods are required to prevent overfitting of a new prediction model. Combining all data with imputation of missing marker values is an attractive option, even if a relatively large marker data set is available

Production of human recombinant proapolipoprotein A-I in Escherichia coli: purification and biochemical characterization

A human liver cDNA library was used to isolate a clone coding for apolipoprotein A-I (Apo A-I). The clone carries the sequence for the prepeptide (18 amino acids), the propeptide (6 amino acids), and the mature protein (243 amino acids). A coding cassette for the proapo A-I molecule was reconstructed by fusing synthetic sequences, chosen to optimize expression and specifying the amino-terminal methionine and amino acids -6 to +14, to a large fragment of the cDNA coding for amino acids 15-243. The module was expressed in pOTS-Nco, an Escherichia coli expression vector carrying the regulatable X P^ promoter, leading to the production of proapolipoprotein A-I at up to 10% of total soluble proteins. The recombinant polypeptide was purified and characterized in terms of apparent molecular mass, isoelectric point, and by both chemical and enzymatic peptide mapping. In addition, it was assayed in vitro for the stimulation of the enzyme lecithin: cholesterol acyltransferase. The data show for the first time that proapo A-I can be produced efficiently in E. coli as a stable and undegraded protein having physical and functional properties indistinguishable from those of the natural product