Impact of lung cancer screening results on participant health-related quality of life and state anxiety in the National Lung Screening Trial

BACKGROUND Low-dose computed tomography (LDCT) lung screening has been associated with a 20% reduction in lung cancer mortality. A major barrier to the adoption of lung screening is the potential negative psychological impact of a false-positive (FP) screen, occurring in 20% to 50% of those screened. The objective of this study was to assess the impact of abnormal findings on health-related quality of life (HRQoL) and anxiety in the American College of Radiology (ACRIN)/National Lung Screening Trial (NLST). METHODS The NLST was a randomized screening trial comparing LDCT with chest X-ray screening (CXR). This study was part of the original protocol. A total of 2812 participants at 16 of 23 ACRIN sites who had baseline HRQoL assessments were asked to complete the Short Form-36 and the State Trait Anxiety Inventory (form Y-1) questionnaires to assess short-term (1 month) and long-term (6 months) effects of screening. FP were lung cancer–free at 1 year, and true-positives (TP) were not. RESULTS Of the total participants, 1024 (36.4%) participants were FP, 63 (2.2%) were TP, 344 (12.2%) had significant incidental findings (SIFs), and 1381 (49.1%) had negative screens. Participants had been randomized to LDCT (n = 1947) and CXR (n = 865). Short-term and long-term HRQoL and state anxiety did not differ across participants with FP, SIF, or negative screens. Short-term and long-term HRQoL were lower and anxiety was higher for TP participants compared to participants with FP, SIF, and negative screens. CONCLUSIONS In a large multicenter lung screening trial, participants receiving a false-positive or SIF screen result experienced no significant difference in HRQoL or state anxiety at 1 or at 6 months after screening relative to those receiving a negative result. Cancer 2014;120:3401–3409. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. In a large multi-center lung screening trial, participants receiving a false positive or significant incidental finding screen result experienced no significant difference in health related quality of life or state anxiety at 1 or at 6 months after screening relative to those receiving a negative result

Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats

<p>Abstract</p> <p>Background</p> <p>Adenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE).</p> <p>Results</p> <p>After SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15–21 days after neuropathy induction, excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP release could result from the conversion of extracellular ATP to adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist, 2-chloro-N⁶-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered ATP release was a consequence of altered DRG metabolism we compared O₂consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O₂at a higher rate than control or contralateral DRG.</p> <p>Conclusion</p> <p>These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation.</p

Arterial properties as determinants of left ventricular mass and fibrosis in severe aortic Stenosis : findings from ACRIN PA 4008

Background-The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement (AVR). Methods and Results-We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR. Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR. Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm(5); P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR (R=-0.51; P=0.0026). The 6-minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time (R=0.52; P=0.01). Conclusions-Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR. Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population

Coronary computed tomography angiography compared with single photon emission computed tomography myocardial perfusion imaging as a guide to optimal medical therapy in patients presenting with stable angina: The RESCUE trial

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of 1.3 (95% CI=0, 1.605). One thousand fifty participants from 44 sites were randomized to CCTA (n=518) or SPECT (n=532). Mean follow-up time was 16.2 (SD 7.9) months. There were no cardiac-related deaths. In patients with a negative CCTA there was 1 acute myocardial infarction; in patients with a negative SPECT examination there were 2 acute myocardial infarctions; and for positive CCTA and SPECT, 1 acute myocardial infarction each. Participants in the CCTA arm had a similar rate of MACE or revascularization compared with those in the SPECT myocardial perfusion imaging arm, (HR, 1.03; 95% CI=0.61-1.75)

Discovery of the Optical Transient of the Gamma Ray Burst 990308

The optical transient of the faint Gamma Ray Burst 990308 was detected by the QUEST camera on the Venezuelan 1-m Schmidt telescope starting 3.28 hours after the burst. Our photometry gives $V = 18.32 \pm 0.07$, $R = 18.14 \pm 0.06$, $B = 18.65 \pm 0.23$, and $R = 18.22 \pm 0.05$ for times ranging from 3.28 to 3.47 hours after the burst. The colors correspond to a spectral slope of close to $f_{\nu} \propto \nu^{1/3}$. Within the standard synchrotron fireball model, this requires that the external medium be less dense than $10^{4} cm^{-3}$, the electrons contain $> 20$ of the shock energy, and the magnetic field energy must be less than 24% of the energy in the electrons for normal interstellar or circumstellar densities. We also report upper limits of $V > 12.0$ at 132 s (with LOTIS), $V > 13.4$ from 132-1029s (with LOTIS), $V > 15.3$ at 28.2 min (with Super-LOTIS), and a 8.5 GHz flux of $< 114 \mu Jy$ at 110 days (with the Very Large Array). WIYN 3.5-m and Keck 10-m telescopes reveal this location to be empty of any host galaxy to $R > 25.7$ and $K > 23.3$. The lack of a host galaxy likely implies that it is either substantially subluminous or more distant than a red shift of $\sim 1.2$.Comment: ApJ Lett submitted, 5 pages, 2 figures, no space for 12 coauthor

Low Background Signal Readout Electronics for the MAJORANA DEMONSTRATOR

The MAJORANA DEMONSTRATOR is a planned 40 kg array of Germanium detectors intended to demonstrate the feasibility of constructing a tonne-scale experiment that will seek neutrinoless double beta decay ($0\nu\beta\beta$) in $^{76}\mathrm{Ge}$. Such an experiment would require backgrounds of less than 1 count/tonne-year in the 4 keV region of interest around the 2039 keV Q-value of the $\beta\beta$ decay. Designing low-noise electronics, which must be placed in close proximity to the detectors, presents a challenge to reaching this background target. This paper will discuss the MAJORANA collaboration's solutions to some of these challenges