Assessment of PI-RADS v2 categories ≥ 3 for diagnosis of clinically significant prostate cancer

Abdominal Radiology - To assess the diagnostic accuracy of PI-RADS v2 categories ≥ 3 to detect clinically significant prostate cancer (csPCa) against histopathology of...     

Development of an in vitro mRNA decay system for Escherichia coli: Poly(A) polymerase I is necessary to trigger degradation

Using a novel Escherichia coli in vitro decay system in which polysomes are the source of both enzymes and mRNA, we demonstrate a requirement for poly(A) polymerase I (PAP I) in mRNA turnover. The in vitro decay of two different mRNAs (trxA and lpp) is triggered by the addition of ATP only when polysomes are prepared from a strain carrying the wild-type gene for PAP I (pcnB⁺). The relative decay rates of these two messages are similar in vitro and in vivo. Poly(A) tails are formed on both mRNAs, but no poly(A) tails are detected on the 3′ end of mature 23S rRNA. The size distribution of poly(A) tails generated in vitro, averaging 50 nt in length, is comparable to that previously reported in vivo. PAP I activity is associated exclusively with the polysomes. Exogenously added PAP I does not restore mRNA decay to PAP I⁻ polysomes, suggesting that, in vivo, PAP I may be part of a multiprotein complex. The potential of this in vitro system for analyzing mRNA decay in E. coli is discussed.     

Unusual viral infections (progressive multifocal leukoencephalopathy and cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem cell rescue and peritransplantation rituximab

Efforts to reduce relapse of non-Hodgkin lymphoma after autologous transplantation have included ex vivo stem cell selection and/or peritransplantation immunotherapy. The late infectious and immunologic consequences of these maneuvers are not well understood, although an increase in early cytomegaloviral disease after CD34(+) stem cell selection and an alteration in immunoglobulin and T-cell recovery after peritransplantation rituximab has been noted. We report the first 2 cases of progressive multifocal leukoencephalopathy caused by JC papovavirus after autologous peripheral blood stem cell transplantation and a case each of cytomegalovirus retinitis and pneumonitis. All 4 patients experienced significant impairment of CD4 T-cell recovery, placing them at risk for these unusual viral infections. The clustering of cases is concerning because all occurred shortly after the introduction of peritransplantation rituximab into treatment protocols (4 of 62 immunotherapy recipients compared with 0 of 276 without; z = 3.595; P <.001), although a direct association with this CD20 B-cell-directed therapy remains speculative.     

Dynamic Medication Adherence Modeling in Primary Prevention of Cardiovascular Disease: A Markov Microsimulation Methods Application

BackgroundReal-world patients’ medication adherence is lower than that of clinical trial patients. Hence, the effectiveness of medications in routine practice may differ.ObjectivesThe study objective was to compare the outcomes of an adherence-naive versus a dynamic adherence modeling framework using the case of statins for the primary prevention of cardiovascular (CV) disease.MethodsStatin adherence was categorized into three state-transition groups on the basis of an epidemiological cohort study. Yearly adherence transitions were incorporated into a Markov microsimulation using TreeAge software. Tracker variables were used to store adherence transitions, which were used to adjust probabilities of CV events over the patient’s lifetime. Microsimulation loops “random walks” estimated the average accrued quality-adjusted life-years (QALYs) and CV events. For each 1,000-patient microsimulations, 10,000 outer loops were performed to reflect second-order uncertainty.ResultsThe adherence-naive model estimated 0.14 CV events avoided per person, whereas the dynamic adherence model estimated 0.08 CV events avoided per person. Using the adherence-naive model, we found that statin therapy resulted in 0.40 QALYs gained over the lifetime horizon on average per person while the dynamic adherence model estimated 0.22 incremental QALYs gained. Subgroup analysis revealed that maintaining high adherence in year 2 resulted in 0.23 incremental QALYs gained as compared with 0.16 incremental QALYs gained when adherence dropped to the lowest level.ConclusionsA dynamic adherence Markov microsimulation model reveals risk reduction and effectiveness that are lower than with an adherence-naive model, and reflective of real-world practice. Such a model may highlight the value of improving or maintaining good adherence.     

Usability Testing of a Sensor-Controlled Digital Game to Engage Older Adults with Heart Failure in Physical Activity and Weight Monitoring

Background  Poor self-management of heart failure (HF) has contributed to poor health outcomes. Sensor-controlled digital games (SCDGs) integrates data from behavior-tracking sensors to trigger progress, rewards, content, and positive feedback in a digital game to motivate real-time behaviors. Objectives  To assess the usability of an SCDG prototype over a week of game-playing among 10 older adults with HF in their homes. Methods  During initial play, participants'' SCDG experiences were observed in their homes using a checklist based on the seven-item Serious Game User Evaluator (SeGUE) instrument. After a week of game-playing, participants completed a survey guided by the Intrinsic Motivation Inventory, to provide their perceptions of the SCDG''s usability. Qualitative analysis via semistructured interview-derived themes on experiences playing the SCDG, perceptions regarding engaging with the SCDG, and any usability issues encountered. Results  Ten HF participants (50% women and 50% White) played the SCDG for an average of 6 out of 7 days. Nine found the SCDG to be interesting, satisfying, and easy to play. The average step count over a week was 4,117 steps (range: 967–9,892). Average adherence with weight monitoring was 5.9 days in a week. Qualitative analysis yielded outcomes regarding attitudes toward SCDG, and barriers and facilitators that influenced participants'' engagement with the SCDG. Conclusion  To the best of the authors'' knowledge, this usability and feasibility study is the first to report an SCDG designed to improve HF self-management behaviors of older adults in their homes. Future research should consider several issues, such as user profiles, prior game-playing experiences, and network conditions most suitable for connected health interventions for older adults living in the community.