Inference of Long-Term Screening Outcomes for Individuals with Screening Histories

<p>We develop a probability model for evaluating long-term outcomes due to regular screening that incorporates the effects of prior screening examinations. Previous models assume that individuals have no prior screening examinations at their current ages. Due to current widespread medical emphasis on screening, the consideration of screening histories is essential, particularly in assessing the benefit of future screening examinations given a certain number of previous negative screens. Screening participants are categorized into four mutually exclusive groups: <i>symptom-free-life, no-early-detection, true-early-detection</i>, and <i>overdiagnosis</i>. For each case, we develop models that incorporate a person’s current age, screening history, expected future screening frequency, screening test sensitivity, and other factors, and derive the probabilities of occurrence for the four groups. The probability of overdiagnosis among screen-detected cases is derived and estimated. The model applies to screening for any disease or condition; for concreteness, we focus on female breast cancer and use data from the study conducted by the Health Insurance Plan of Greater New York (HIP) to estimate these probabilities and corresponding credible intervals. The model can provide policy makers with important information regarding ranges of expected lives saved and percentages of true-early-detection and overdiagnosis among the screen-detected cases.</p

Plasma extraction at multiple time points.

<p><b>Bold</b> = statistically significant.</p><p>Plasma extraction at multiple time points.</p

Results of ANOVA analysis for initial microRNA selection.

<p>Abbreviations: CRC, colorectal cancer; BC, breast cancer; PC, pancreatic cancer; LC, lung cancer; CAA, colorectal advanced adenoma.</p><p>Results of ANOVA analysis for initial microRNA selection.</p

The phases and components of a PCR curves: (1) baseline, (2) exponential phase, (3) linear phase, (4) plateau phase, and (5) cycle threshold.

<p>The phases and components of a PCR curves: (1) baseline, (2) exponential phase, (3) linear phase, (4) plateau phase, and (5) cycle threshold.</p

Inter-operator variability with two different extraction methods.

<p>Differences in ΔΔCT between Qiagen miRNeasy with RNA carrier and no pre-amplification and Trizol LS with pre-amplification.</p><p>* |ΔΔCT| = Absolute Value [Operator 1 ΔCT—Operator 2 ΔCT].</p><p><b>Bold</b> = statistically significant.</p><p>^a = chi-squared test comparing number of miRNA not expressed using Trizol LS with preamplification as compared to using Qiagen miRNeasy without preamplification.</p><p>Inter-operator variability with two different extraction methods.</p

Total RNA concentration and purity for Trizol LS and Qiagen miRNeasy with RNA yeast carrier.

<p>*p-value for mean total RNA concentration between methods.</p><p>Total RNA concentration and purity for Trizol LS and Qiagen miRNeasy with RNA yeast carrier.</p

Intra-Operator Variability (Duplicates) for the Trizol LS RNA Extraction and Preamplicification Protocol.

<p>^† |ΔCT| = absolute value (mean cycle threshold value for duplicate 1 for the miRNA of interest—mean cycle threshold value for duplicate 2 for the miRNA of interest.</p><p>Intra-Operator Variability (Duplicates) for the Trizol LS RNA Extraction and Preamplicification Protocol.</p

Untersuchungen über die Theorie der isothermen Flächen

<p>A) Receiver operator characteristic (ROC) curve for miR-523,miR-218,miR-142-3p,miR 27a,miR-21. Colorectal cancer (n = 20) vs. Breast cancer +Pancreatic cancer + Lung cancer (n = 30 [10 each group]). B) ROC Curve for miR-523, miR-218, miR-142-3p,miR-27a,miR-376c,miR-374. Colorectal cancer (n = 20) + Colorectal adenoma (n = 10) vs. Breast cancer +Pancreatic cancer + Lung cancer (n = 30 [10 each group]).</p

Systematic review: 74 plasma miRNA publications July 1, 2013—June 30, 2014.

<p>⁺ Some manuscripts utilized more than one method of RNA extraction.</p><p>* Some manuscripts used both an internal and external reference.</p><p>^ψ Many manuscripts used multiple methods of statistical analysis.</p><p>Systematic review: 74 plasma miRNA publications July 1, 2013—June 30, 2014.</p

Heat map showing expression of 11 miRNA in plasma of 16 patients with colorectal adenoma prior to treatment and in plasma of 16 controls.

<p>Color gradation refers to delta Ct values with RNU6 as reference. Negative values represent over-expression of the target miRNA in comparison to the reference miRNA (RNU6).</p