Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of ...recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (<11.2% coefficient of variation).
Care transition models are structured approaches used to ensure the smooth transfer of patients between health care settings or levels of care, but none currently are tailored to the surgical ...patient. Tailoring care transition models to the unique needs of surgical patients may lead to significant improvements in surgical outcomes and reduced care fragmentation. The first step to developing surgical care transition models is to understand the surgical discharge process.
To map the surgical discharge process in a sample of US hospitals and identify key components and potential challenges specific to a patient's discharge after surgery.
This qualitative study followed a cognitive task analysis framework conducted between January 1, 2022, and April 1, 2023, in Veterans Health Administration (VHA) hospitals. Observations (n = 16) of discharge from inpatient care after a surgical procedure were conducted in 2 separate VHA surgical units. Interviews (n = 13) were conducted among VHA health care professionals nationwide.
Postoperative hospital discharge.
Data were coded according to the principles of thematic analysis, and a swim lane process map was developed to represent the study findings.
At the hospitals in this study, the discharge process observed for a surgical patient involved multidisciplinary coordination across the surgery team, nursing team, case managers, dieticians, social services, occupational and physical therapy, and pharmacy. Important components for a surgical discharge that were not incorporated in the current care transition models included wound care education and supplies; pain control; approvals for nonhome postdischarge locations; and follow-up plans for wounds, ostomies, tubes, and drains at discharge. Potential challenges to the surgical discharge process included social situations (eg, home environment and caregiver availability), team communication issues, and postdischarge care coordination.
These findings suggest that current and ongoing studies of discharge care transitions for a patient after surgery should consider pain control; wounds, ostomies, tubes, and drains; and the impact of challenging social situations and interdisciplinary team coordination on discharge success.
Objective
Designing practical decision support tools and other health care technology in health services research relies on a clear understanding of the cognitive processes that underlie the use of ...these tools. Unfortunately, methods to explore cognitive processes are rarely used in health services research. Thus, the objective of this manuscript is to introduce cognitive task analysis (CTA), a family of methods to study cognitive processes involved in completing a task, to a health services research audience. This methods article describes CTA procedures, proposes a framework for their use in health services research studies, and provides an example of its application in a pilot study.
Data Sources and Study Setting
Observations and interviews of health care providers involved in discharge planning at six hospitals in the Veterans Health Administration.
Study Design
Qualitative study of discharge planning using CTA.
Data Collection/Extraction Methods
Data were collected from structured observations and semi‐structured interviews using the Critical Decision Method and analyzed using thematic analysis.
Principal Findings
We developed an adaptation of CTA that could be used in a clinical environment to describe clinical decision‐making and other cognitive processes. The adapted CTA framework guides the user through four steps: (1) Planning, (2) Environmental Analysis, (3) Knowledge Elicitation, and (4) Analyses and Results. This adapted CTA framework provides an iterative and systematic approach to identifying and describing the knowledge, expertise, thought processes, procedures, actors, goals, and mental strategies that underlie completing a clinical task.
Conclusions
A better understanding of the cognitive processes that underly clinical tasks is key to developing health care technology and decision‐support tools that will have a meaningful impact on processes of care and patient outcomes. Our adapted framework offers a more rigorous and detailed method for identifying task‐related cognitive processes in implementation studies and quality improvement. Our adaptation of this underutilized qualitative research method may be helpful to other researchers and inform future research in health services research.
Small molecule phosphodiesterase (PDE) 4 inhibitors have long been known to show therapeutic benefit in various preclinical models of psychiatric and neurologic diseases because of their ability to ...elevate cAMP in various cell types of the central nervous system. Despite the registration of the first PDE4 inhibitor, roflumilast, for the treatment of chronic obstructive pulmonary disease, the therapeutic potential of PDE4 inhibitors in neurologic diseases has never been fulfilled in the clinic due to severe dose-limiting side effects such as nausea and vomiting. In this study, we describe the detailed pharmacological characterization of GSK356278 5-(5-((2,4-dimethylthiazol-5-yl)methyl)-1,3,4-oxadiazol-2-yl)-1-ethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo3,4-bpyridin-4-amine, a potent, selective, and brain-penetrant PDE4 inhibitor that shows a superior therapeutic index to both rolipram and roflumilast in various preclinical species and has potential for further development in the clinic for the treatment of psychiatric and neurologic diseases. GSK356278 inhibited PDE4B enzyme activity with a pIC50 of 8.8 and bound to the high-affinity rolipram binding site with a pIC50 of 8.6. In preclinical models, the therapeutic index as defined in a rodent lung inflammation model versus rat pica feeding was >150 compared with 0.5 and 6.4 for rolipram and roflumilast, respectively. In a model of anxiety in common marmosets, the therapeutic index for GSK356278 was >10 versus <1 for rolipram. We also demonstrate that GSK356278 enhances performance in a model of executive function in cynomolgus macaques with no adverse effects, a therapeutic profile that supports further evaluation of GSK356278 in a clinical setting.
Current trends suggest that academia may be behind the curve in delivering effective Business Intelligence programs and course offerings to students. In December 2009 and 2010, the AIS Special ...Interest Group on Decision Support, Knowledge and Data Management Systems (SIGDSS) and the Teradata University Network (TUN) cosponsored the Business Intelligence Congresses and conducted surveys to improve the understanding of the state of BI in academia. This panel report describes the key findings and best practices that were identified. The article also serves as a “call to action” for universities regarding the need to close a widening gap between the BI skills of university graduates in Information Systems and other fields and BI market needs. The IS field is well positioned to be the leader in creating the next generation BI workforce. To do so, it is important for IS to begin moving on this opportunity now. We believe the necessary first step is for BI and IS leaders to advance the BI curriculum.
In 1957--long before colleges awarded degrees in creative
nonfiction and back when newspaper writing's reputation was tainted
by the fish it wrapped--Princeton began honoring talented literary
...journalists. Since then, fifty-nine of the finest, most dedicated,
and most decorated nonfiction writers have held the Ferris and
McGraw professorships. This monumental volume harbors their
favorite and often most influential works. Each contribution is
rewarding reading, and collectively the selections validate
journalism's ascent into the esteem of the academy and the reading
public. Necessarily eclectic and delightfully idiosyncratic, the
fifty-nine pieces are long and short, political and personal, comic
and deadly serious. Students will be provoked by William Greider's
pointed critique of the democracy industry, eerily entertained by
Leslie Cockburn's fraternization with the Cali cartel, inspired by
David K. Shipler's thoughts on race, unsettled by Haynes Johnson's
account of Bay of Pigs survivors, and moved by Lucinda Frank's
essay on a mother fighting to save a child born with birth defects.
Many of the essays are finely crafted portraits: Charlotte Grimes's
biography of her grandmother, Blair Clark's obituary for Robert
Lowell, and Jane Kramer's affecting story of a woman hero of the
French Resistance. Other contributions to savor include Harrison
Salisbury on the siege of Leningrad, Landon Jones on the 1950s,
Christopher Wren on Soviet mountaineering, James Gleick on
technology, Gloria Emerson on Vietnam, Gina Kolata on Fermat's last
theorem, and Roger Mudd on the media. Whether approached
chronologically, thematically, randomly, or, as the editors order
them, more intuitively, each suggests a perfect evening reading.
Designed for students as well as general readers, The Princeton
Anthology of Writing splendidly attests to the elegance,
eloquence, and endurance of fine nonfiction.
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