Implementing a Telehealth Shared Counseling and Decision-Making Visit for Lung Cancer Screening in a Veterans Affairs Medical Center.

Background: Veterans suffer substantial morbidity and mortality from lung cancer. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce mortality. Guidelines recommend counseling and shared decision-making (SDM) to address the benefits and harms of screening and the importance of tobacco cessation before patients undergo screening. Observations: We implemented a centralized LCS program at the Iowa City Veterans Affairs Medical Center with a nurse program coordinator (NPC)-led telephone visit. Our multidisciplinary team ensured that veterans referred from primary care met eligibility criteria, that LDCT results were correctly coded by radiology, and that pulmonary promptly evaluated abnormal LDCT. The NPC mailed a decision aid to the veteran and scheduled a SDM telephone visit. We surveyed veterans after the visit using validated measures to assess knowledge, decisional conflict, and quality of decision making. We conducted 105 SDM visits, and 91 veterans agreed to LDCT. Overall, 84% of veterans reported no decisional conflict, and 59% reported high-quality decision making. While most veterans correctly answered questions about the harms of radiation, false-positive results, and overdiagnosis, few knew when to stop screening, and most overestimated the benefit of screening and the predictive value of an abnormal scan. Tobacco cessation interventions were offered to 72 currently smoking veterans. Conclusions: We successfully implemented an LCS program that provides SDM and tobacco cessation support using a centralized telehealth model. While veterans were confident about screening decisions, knowledge testing indicated important deficits, and many did not engage meaningfully in SDM. Clinicians should frame the decision as patient centered at the time of referral, highlight the importance of SDM, and be able to provide adequate decision support.

Applying a Text-Search Algorithm to Radiology Reports Can Find More Patients With Pulmonary Nodules Than Radiology Coding Alone.

INTRODUCTION: Chest imaging often incidentally finds indeterminate nodules that need to be monitored to ensure early detection of lung cancers. Health care systems need effective approaches for identifying these lung nodules. We compared the diagnostic performance of 2 approaches for identifying patients with lung nodules on imaging studies (chest/abdomen): (1) relying on radiologists to code imaging studies with lung nodules; and (2) applying a text search algorithm to identify references to lung nodules in radiology reports. METHODS: We assessed all radiology studies performed between January 1, 2016 and November 30, 2016 in a single Veterans Health Administration hospital. We first identified imaging reports with a diagnostic code for a pulmonary nodule. We then applied a text search algorithm to identify imaging reports with key words associated with lung nodules. We reviewed medical records for all patients with a suspicious radiology report based on either search strategy to confirm the presence of a lung nodule. We calculated the yield and the positive predictive value (PPV) of each search strategy for finding pulmonary nodules. RESULTS: We identified 12,983 imaging studies with a potential lung nodule. Chart review confirmed 8,516 imaging studies with lung nodules, representing 2,912 unique patients. The text search algorithm identified all the patients with lung nodules identified by the radiology coding (n = 1,251) as well as an additional 1,661 patients. The PPV of the text search was 72% (2,912/4,071) and the PPV of the radiology code was 92% (1,251/1,363). Among the patients with nodules missed by radiology coding but identified by the text search algorithm, 130 had lung nodules > 8 mm in diameter. CONCLUSIONS: The text search algorithm can identify additional patients with lung nodules compared to the radiology coding; however, this strategy requires substantial clinical review time to confirm nodules. Health care systems adopting nodule-tracking approaches should recognize that relying only on radiology coding might miss clinically important nodules.

Partial activation precedes apoptotic death in T cells harboring an IAN gene mutation.

The Biobreeding diabetes-prone rat suffers from a profound peripheral lymphopenia and yet succumbs to a T cell-dependent autoimmune disease. Lymphopenia segregates with a mutated chromosomal locus, termed lyp, recently identified as a frameshift mutation in IAN4. Others have correlated loss of IAN4 function with decreased mitochondrial integrity resulting in T cell apoptosis. Here we report that IAN4-/- T cells enter a state similar to that of partial activation wherein they down-regulate CD62L and undergo incomplete blasting yet do not progress through mitosis. When given a strong stimulus, this partial activation phenotype can be overcome. This phenotype can be recapitulated in wild-type T cells through suboptimal stimulation. The phenotype is not simply a reaction to the lymphopenic environment, as spontaneous CD62L down-regulation occurs in mature single-positive medullary thymocytes that develop within a non-lymphopenic environment, and normal T cells do not undergo similar blasting when parked in a lymphopenic environment. Finally, we show that IAN4-/- T cells are more readily triggered via TCR stimulation. Thus, in addition to their role in apoptosis, IAN family members may also play a role in regulating the T cell activation state through modulation of TCR signaling strength.

Superoxide mediates the actions of angiotensin II in the central nervous system.

Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CNS. Recently, a novel signaling mechanism for Ang II involving reactive oxygen species (ROS) has been identified in a variety of peripheral tissues, but the involvement of ROS as second messengers in Ang II-mediated signaling in the CNS has not been reported. The hypothesis that superoxide is a key mediator of the actions of Ang II in the CNS was tested in mice using adenoviral vector-mediated expression of superoxide dismutase (AdSOD). Changes in blood pressure, heart rate, and drinking elicited by injection of Ang II in the CNS were abolished by prior treatment with AdSOD in the brain, whereas the cardiovascular responses to carbachol, another central vasopressor agent, were unaffected. In addition, Ang II stimulated superoxide generation in primary CNS cell cultures, and this was prevented by the Ang II receptor (Ang II type 1 subtype) antagonist losartan or AdSOD. These results identify a novel signaling mechanism mediating the actions of Ang II in the CNS. Dysregulation of this signaling cascade may be important in hypertension and heart failure triggered by Ang II acting in the CNS.

Brain-selective overexpression of angiotensin (AT1) receptors causes enhanced cardiovascular sensitivity in transgenic mice.

To examine the physiological importance of brain angiotensin II type 1 (AT1) receptors, we developed a novel transgenic mouse model with rat AT1a receptors targeted selectively to neurons of the central nervous system (CNS). A transgene consisting of 2.8 kb of the rat neuron-specific enolase (NSE) 5' flanking region fused to a cDNA encoding the full open-reading frame of the rat AT1a receptor was constructed and transgenic mice (NSE-AT1a) were generated. Two of six transgenic founder lines exhibited brain-selective expression of the transgene at either moderate or high levels. Immunohistochemistry revealed widespread distribution of AT1 receptors in neurons throughout the CNS. This neuron-targeted overexpression of AT1a receptors resulted in enhanced cardiovascular responsiveness to intracerebroventricular (ICV) angiotensin II (Ang II) injection but not to other central pressor agents, demonstrating functional overexpression of the transgene in NSE-AT1a mice. Interestingly, baseline blood pressure (BP) was not elevated in either transgenic line. However, blockade of central AT1 receptors with ICV losartan caused significant falls in basal BP in NSE-AT1a mice but had no effect in nontransgenic controls. These results suggest that whereas there is an enhanced contribution of central AT1 receptors to the maintenance of baseline BP in NSE-AT1a mice, particularly effective baroreflex buffering prevents hypertension in this model. Used both independently, and in conjunction with mice harboring gene-targeted deletions of AT1a receptors, this new model will permit quantitative and relevant investigations of the role of central AT1a receptors in cardiovascular homeostasis in health and disease.