The Impact of Different Screening Model Structures on Cervical Cancer Incidence and Mortality Predictions: The Maximum Clinical Incidence Reduction (MCLIR) Methodology

Background. To interpret cervical cancer screening model results, we need to understand the influence of model structure and assumptions on cancer incidence and mortality predictions. Cervical cancer cases and deaths following screening can be attributed to 1) (precancerous or cancerous) disease that occurred after screening, 2) disease that was present but not screen detected, or 3) disease that was screen detected but not successfully treated. We examined the relative contributions of each of these using 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models. Methods. The maximum clinical incidence reduction (MCLIR) method compares changes in the number of clinically detected cervical cancers and mortality among 4 scenarios: 1) no screening, 2) one-time perfect screening at age 45 that detects all existing disease and delivers perfect (i.e., 100% effective) treatment of all screen-detected disease, 3) one-time realistic-sensitivity cytological screening and perfect treatment of all screen-detected disease, and 4) one-time realistic-sensitivity cytological screening and realistic-effectiveness treatment of all screen-detected disease. Results. Predicted incidence reductions ranged from 55% to 74%, and mortality reduction ranged from 56% to 62% within 15 years of follow-up for scenario 4 across models. The proportion of deaths due to disease not detected by screening differed across the models (21%–35%), as did the failure of treatment (8%–16%) and disease occurring after screening (from 1%–6%). Conclusions. The MCLIR approach aids in the interpretation of variability across model results. We showed that the reasons why screening failed to prevent cancers and deaths differed between the models. This likely reflects uncertainty about unobservable model inputs and structures; the impact of this uncertainty on policy conclusions should be examined via comparing findings from different well-calibrated and validated model platforms

Effect of time to diagnostic testing for breast, cervical, and colorectal cancer screening abnormalities on screening efficacy: A modeling study

Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices. Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to follow-up for breast, cervical, and colorectal cancers was increased. Estimates were based on four independently developed microsimulation models that each simulated the life course of adults eligible for breast (women ages 50–74 years), cervical (women ages 21–65 years), or colorectal (adults ages 50–75 years) cancer screening. We assumed screening based on biennial mammography for breast cancer, triennial Papanicolaou testing for cervical cancer, and annual fecal immunochemical testing for colorectal cancer. For each cancer type, we simulated diagnostic testing immediately and at 3, 6, and 12 months after an abnormal screening exam. Results: We found declines in screening benefit with longer times to diagnostic testing, particularly for breast cancer screening. Compared to immediate diagnostic testing, testing at 3 months resulted in reduced screening benefit, with fewer undiscounted life years gained per 1,000 screened (breast: 17.3%, cervical: 0.8%, colorectal: 2.0% and 2.7%, from two colorectal cancer models), fewer cancers prevented (cervical: 1.4% fewer, colorectal: 0.5% and 1.7% fewer, respectively), and, for breast and colorectal cancer, a less favorable stage distribution. Conclusions: Longer times to diagnostic testing after an abnormal screening test can decrease screening effectiveness, but the impact varies substantially by cancer type. Impact: Understanding the impact of time to diagnostic testing on screening effectiveness can help inform quality improvement efforts. Cancer Epidemiol Biomarkers Prev; 27(2); 158–64. 2017 AACR

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world’s countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.</p

JET Tokamak, preparation of a safety case for tritium operations

A new Safety Case is required to permit tritium operations on JET during the forthcoming DTE2 campaign.The outputs, benefits and lessons learned associated with the production of this Safety Case are presented. The changes that have occurred to the Safety Case methodology since the last JET tritium Safety Case are reviewed. Consideration is given to the effects of modifications, particularly ITER related changes, made to the JET and the impact these have on the hazard assessments as well as normal operations. Several specialized assessments, including recent MELCOR modelling, have been undertaken to support the production of this Safety Case and the impact of these assessments is outlined. Discussion of the preliminary actions being taken to progress implementation of this Safety Case is provided, highlighting new methods to improve the dissemination of the key Safety Case results to the plant operators. Finally, the work required to complete this Safety Case, before the next tritium campaign, is summarized