Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties and gene expression

BACKGROUND: Introduction of cDNA or genomic clones of the tumor suppressor in lung cancer 1 (TSLC1) gene into the non-small cell lung cancer line, A549, reverses tumorigenic growth properties of these cells. These results and the observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1 functions as a critical switch mediating repression of tumorigenesis. RESULTS: To investigate this mechanism, we compared growth properties of A549 with the TSLC1-containing derivative. We found a G1/S phase transition delay in 12.2. Subtractive hybridization, quantitative PCR, and TranSignal Protein/DNA arrays were used to identify genes whose expression changed when TSLC1 was up-regulated. Members of common G1/S phase regulatory pathways such as TP53, MYC, RB1 and HRAS were not differentially expressed, indicating that TSLC1 may function through an alternative pathway(s). A number of genes involved in cell proliferation and tumorigenesis were differentially expressed, notably genes in the Ras-induced senescence pathway. We examined expression of several of these key genes in human tumors and normal lung tissue, and found similar changes in expression, validating the physiological relevance of the A549 and 12.2 cell lines. CONCLUSION: Gene expression and cell cycle differences provide insights into potential downstream pathways of TSLC1 that mediate the suppression of tumor properties in A549 cells

Modelling care quality for patients after a transient ischaemic attack within the US Veterans Health Administration

Objective Timely preventive care can substantially reduce risk of recurrent vascular events or death after a transient ischaemic attack (TIA). Our objective was to understand patient and facility factors influencing preventive care quality for patients with TIA in the US Veterans Health Administration (VHA). Methods We analysed administrative data from a retrospective cohort of 3052 patients with TIA cared for in the emergency department (ED) or inpatient setting in 110 VHA facilities from October 2010 to September 2011. A composite quality indicator (QI score) pass rate was constructed from four process-related quality measures—carotid imaging, brain imaging, high or moderate potency statin and antithrombotic medication, associated with the ED visit or inpatient admission after the TIA. We tested a multilevel structural equation model where facility and patient characteristics, inpatient admission, and neurological consultation were predictors of the resident’s composite QI score. Results Presenting with a speech deficit and higher Charlson Comorbidity Index (CCI) were positively related to inpatient admission. Being admitted increased the likelihood of neurology consultation, whereas history of dementia, weekend arrival and a higher CCI score made neurological consultation less likely. Speech deficit, higher CCI, inpatient admission and neurological consultation had direct positive effects on the composite quality score. Patients in facilities with fewer full-time equivalent neurology staff were less likely to be admitted or to have a neurology consultation. Facilities having greater organisational complexity and with a VHA stroke centre designation were more likely to provide a neurology consultation. Conclusions Better TIA preventive care could be achieved through increased inpatient admissions, or through enhanced neurology and other care resources in the ED and during follow-up care

Comparison of performance achievement award recognition with primary stroke center certification for acute ischemic stroke care.

BackgroundHospital certification and recognition programs represent 2 independent but commonly used systems to distinguish hospitals, yet they have not been directly compared. This study assessed acute ischemic stroke quality of care measure conformity by hospitals receiving Primary Stroke Center (PSC) certification and those receiving the American Heart Association's Get With The Guidelines-Stroke (GWTG-Stroke) Performance Achievement Award (PAA) recognition.Methods and resultsThe patient and hospital characteristics as well as performance/quality measures for acute ischemic stroke from 1356 hospitals participating in the GWTG-Stroke Program 2010-2012 were compared. Hospitals were classified as PAA+/PSC+ (hospitals n = 410, patients n = 169,302), PAA+/PSC- (n = 415, n = 129,454), PAA-/PSC+ (n = 88, n = 26,386), and PAA-/PSC- (n = 443, n = 75,565). A comprehensive set of stroke measures were compared with adjustment for patient and hospital characteristics. Patient characteristics were similar by PAA and PSC status but PAA-/PSC- hospitals were more likely to be smaller and nonteaching. Measure conformity was highest for PAA+/PSC+ and PAA+/PSC- hospitals, intermediate for PAA-/PSC+ hospitals, and lowest for PAA-/PSC- hospitals (all-or-none care measure 91.2%, 91.2%, 84.3%, and 76.9%, respectively). After adjustment for patient and hospital characteristics, PAA+/PSC+, PAA+/PSC-, and PAA-/PSC+ hospitals had 3.15 (95% CIs 2.86 to 3.47); 3.23 (2.93 to 3.56) and 1.72 (1.47 to 2.00), higher odds for providing all indicated stroke performance measures to patients compared with PAA-/PSC- hospitals.ConclusionsWhile both PSC certification and GWTG-Stroke PAA recognition identified hospitals providing higher conformity with care measures for patients hospitalized with acute ischemic stroke, PAA recognition was a more robust identifier of hospitals with better performance

Atmospheric Concentrations and Deposition of Trichloroacetic Acid in Scotland: Results from a 2-Year Sampling Campaign

The first long-term concurrent measurements of trichloroacetic acid (TCA) in rainwater, in cloudwater, and in air (both gas and particle phase) are reported. Measurements were made weekly between June 1998 and April 2000 at a rural forested upland site in SE Scotland. Rainwater TCA concentration did not differ significantly between two elevations (602 and 275 m asl), with precipitation-weighted mean values of 0.77 and 0.70 mu g L-1, respectively ( n> 75). The precipitation-weighted mean concentration of TCA in cloudwater at the highest elevation was 0.92 mu g L-1, yielding an average cloudwater enrichment factor of 1.2, considerably lower than for other inorganic ions measured. Rainwater and cloudwater TCA concentrations did not vary systematically with season. Since wet precipitation depth also did not vary systematically with season, the wet deposition fluxes of TCA were likewise invariant (annual fluxes at the highest elevation of 880 and 130 mu g m-2, respectively, for rain and cloud interception to spruce forest). Weekly integrated concentrations of TCA in air (gas and particle) were very low (median 25 pgm-3, range<LOD- 110 pg m-3). The estimated upper limit for annual dry deposition of TCA at this site was 20 mu g m-2, assuming a deposition velocity of 2 cm s-1. Concentrations of TCA in air correlated reasonably strongly with concentrations in rainwater, with a partition ratio approximately equal to the Henry’s law coefficient. On average, only about 23% of TCA measured in Edinburgh air was associated with the particle phase. These measurements are consistent with the observed high scavenging ratio of TCA (ratio of concentration in air to concentration in rainwater). Overall, these data confirm that the atmosphere is an important source of TCA to the environment and that precipitation is the dominant transfer mechanism. In line with previous work, the atmospheric deposition flux is greater than expected from the current understanding of atmospheric production of TCA from anthropogenic precursors. It is suggested that aqueous-phase processes could lead to greater atmospheric conversion of chlorinated solvent precursors to TCA than is currently accepted

Long-Term Exposure of Sitka Spruce Seedlings to Trichloroacetic Acid

Trichloroacetic acid (TCA) has been implicated as an airborne pollutant responsible for adverse effects on forest health. There is considerable debate as to whether TCA observed in trees and forest soils is derived from atmospheric deposition or from in situ production. This experiment reports the results from treating 4-year-old Sitka spruce ( Picea sitchensis(Bong.) Carr) plants in a greenhouse over a growing season with TCA supplied either to the soil or to the foliage at concentrations of 10 and 100 ng mL-1. Similar uptake of TCA by needles was observed for both modes of treatment, with significant accumulation of TCA (300 ng g-1 dry wt) at the higher concentration. Larger concentrations in stem tissue were seen for the foliar-applied TCA (280 ng g-1) than for the soil-applied TCA (70 ng g-1), suggesting that direct stem uptake may be important. Six months after treatments stopped, TCA concentrations in the needles of plants exposed to 100 ng mL-1 TCA were still enhanced, showing that biological degradation of TCA in needles was slow over the winter. By contrast, no significant enhancement of TCA in soil could be detected in the directly treated soils even during the experiment. The protein content of needles treated with the higher concentration of TCA by either route was significantly smaller than for the controls, but there was no effect of TCA on the conjugation of 1-chloro-2,4-dinitrobenzene in roots nor on the conjugation of 1,2-dichloro-4-nitrobenzene in needles

Processes of Care Associated With Risk of Mortality and Recurrent Stroke Among Patients With Transient Ischemic Attack and Nonsevere Ischemic Stroke

Importance: Early evaluation and management of patients with transient ischemic attack (TIA) and nonsevere ischemic stroke improves outcomes. Objective: To identify processes of care associated with reduced risk of death or recurrent stroke among patients with TIA or nonsevere ischemic stroke. Design, Setting, and Participants: This cohort study included all patients with TIA or nonsevere ischemic stroke at Department of Veterans Affairs emergency department or inpatient settings from October 2010 to September 2011. Multivariable logistic regression was used to model associations of processes of care and without-fail care, defined as receiving all guideline-concordant processes of care for which patients are eligible, with risk of death and recurrent stroke. Data were analyzed from March 2018 to April 2019. Main Outcomes and Measures: Risk of all-cause mortality and recurrent ischemic stroke at 90 days and 1 year was calculated. Overall, 28 processes of care were examined. Without-fail care was assessed for 6 processes: brain imaging, carotid artery imaging, hypertension medication intensification, high- or moderate-potency statin therapy, antithrombotics, and anticoagulation for atrial fibrillation. Results: Among 8076 patients, the mean (SD) age was 67.8 (11.6) years, 7752 patients (96.0%) were men, 5929 (73.4%) were white, 474 (6.1%) had a recurrent ischemic stroke within 90 days, 793 (10.7%) had a recurrent ischemic stroke within 1 year, 320 (4.0%) died within 90 days, and 814 (10.1%) died within 1 year. Overall, 9 processes were independently associated with lower odds of both 90-day and 1-year mortality after adjustment for multiple comparisons: carotid artery imaging (90-day adjusted odds ratio [aOR], 0.49; 95% CI, 0.38-0.63; 1-year aOR, 0.61; 95% CI, 0.52-0.72), antihypertensive medication class (90-day aOR, 0.58; 95% CI, 0.45-0.74; 1-year aOR, 0.70; 95% CI, 0.60-0.83), lipid measurement (90-day aOR, 0.68; 95% CI, 0.51-0.90; 1-year aOR, 0.64; 95% CI, 0.53-0.78), lipid management (90-day aOR, 0.46; 95% CI, 0.33-0.65; 1-year aOR, 0.67; 95% CI, 0.53-0.85), discharged receiving statin medication (90-day aOR, 0.51; 95% CI, 0.36-0.73; 1-year aOR, 0.70; 95% CI, 0.55-0.88), cholesterol-lowering medication intensification (90-day aOR, 0.47; 95% CI, 0.26-0.83; 1-year aOR, 0.56; 95% CI, 0.41-0.77), antithrombotics by day 2 (90-day aOR, 0.56; 95% CI, 0.40-0.79; 1-year aOR, 0.69; 95% CI, 0.55-0.87) or at discharge (90-day aOR, 0.59; 95% CI, 0.41-0.86; 1-year aOR, 0.69; 95% CI, 0.54-0.88), and neurology consultation (90-day aOR, 0.67; 95% CI, 0.52-0.87; 1-year aOR, 0.74; 95% CI, 0.63-0.87). Anticoagulation for atrial fibrillation was associated with lower odds of 1-year mortality only (aOR, 0.59; 95% CI, 0.40-0.85). No processes were associated with reduced risk of recurrent stroke after adjustment for multiple comparisons. The rate of without-fail care was 15.3%; 1216 patients received all guideline-concordant processes of care for which they were eligible. Without-fail care was associated with a 31.2% lower odds of 1-year mortality (aOR, 0.69; 95% CI, 0.55-0.87) but was not independently associated with stroke risk. Conclusions and Relevance: Patients who received 6 readily available processes of care had lower adjusted mortality 1 year after TIA or nonsevere ischemic stroke. Clinicians caring for patients with TIA and nonsevere ischemic stroke should seek to ensure that patients receive all guideline-concordant processes of care for which they are eligible

Opening Pandora’s Box From Readmissions to Transitional Care Patient-Centered Outcome Measures

Background: Measuring the effectiveness of transitional care interventions has historically relied on health care utilization as the primary outcome. Although the Care Transitions Measure was the first outcome measure specifically developed for transitional care, its applicability beyond the hospital-to-home transition is limited. There is a need for patient-centered outcome measures (PCOMs) to be developed for transitional care settings (ie, TC-PCOMs) to ensure that outcomes are both meaningful to patients and relevant to the particular care transition. The overall objective of this paper is to describe the opportunities and challenges of integrating TC-PCOMs into research and practice. Methods and Results: This narrative review was conducted by members of the Patient-Centered Outcomes Research Institute (PCORI) Transitional Care Evidence to Action Network. We define TC-PCOMs as outcomes that matter to patients because they account for their individual experiences, concerns, preferences, needs, and values during the transition period. The cardinal features of TC-PCOMs should be that they are developed following direct input from patients and stakeholders and reflect their lived experience during the transition in question. Although few TC-PCOMs are currently available, existing patient-reported outcome measures could be adapted to become TC-PCOMs if they incorporated input from patients and stakeholders and are validated for the relevant care transition. Conclusion: Establishing validated TC-PCOMs is crucial for measuring the responsiveness of transitional care interventions and optimizing care that is meaningful to patients

Care Trajectories of Veterans in the Twelve Months following Hospitalization for Acute Ischemic Stroke

Background—Recovery after a stroke varies greatly between individuals and is reflected by wide variation in the use of institutional and home care services. This study sought to classify veterans according to their care trajectories in the 12 months after hospitalization for ischemic stroke. Methods and Results—The sample consisted of 3811 veterans hospitalized for ischemic stroke in Veterans Health Administration facilities in 2007. Three outcomes—nursing home care, home care, and mortality—were modeled jointly >12 months using latent class growth analysis. Data on Veterans’ care use and cost came from the Veterans Administration and Medicare. Covariates included stroke severity (National Institutes of Health Stroke Scale), functional status (functional independence measure score), age, marital status, chronic conditions, and prestroke ambulation. Five care trajectories were identified: 49% of Veterans had Rapid Recovery with little or no use of care; 15% had a Steady Recovery with initially high nursing home or home care that tapered off; 9% had Long-Term Home Care; 13% had Long-Term Nursing Home Care; and 14% had an Unstable trajectory with multiple transitions between long-term and acute care settings. Care use was greatest for individuals with more severe strokes, lower functioning at hospital discharge, and older age. Average annual costs were highest for individuals with the Long-Term Nursing Home trajectory ($63 082), closely followed by individuals with the Unstable trajectory ($58 720). Individual with the Rapid Recovery trajectory had the lowest costs ($9271). Conclusions—Care trajectories after stroke were associated with stroke severity and functional dependency and they had a dramatic impact on subsequent costs