Smoking cessation services and shared decision-making practices among lung cancer screening facilities: A cross-sectional study.

BACKGROUND: Little is known about how screening facilities are meeting the requirements for the reimbursement of lung cancer screening from the Centers for Medicare & Medicaid Services (CMS), including 1) the collection and submission of data to the CMS-approved registry (American College of Radiology [ACR] Lung Cancer Screening Registry), 2) the verification of a counseling and shared decision-making (SDM) visit having occurred as part of the written order for lung cancer screening with low-dose computed tomography, and 3) the offering of smoking cessation interventions. METHODS: The authors identified facilities in a southwestern state that were listed by either the ACR Lung Cancer Screening Registry or the GO2 Foundation Centers of Excellence. To select facilities, they used 2 purposive sampling approaches: maximum variation sampling and snowball sampling. They surveyed facilities from February to November 2019. RESULTS: There were 87 facilities contacted, and a total of 63 facilities representing 32 counties across Texas completed the survey. Nearly all facilities used Lung-RADS to classify nodules (92%; n = 58) and submitted data to a CMS-approved registry (92%; n = 57). Most facilities verified that the counseling and SDM visit had occurred (86%; n = 54). Although slightly more than half of the facilities reported always providing self-help cessation materials (68%; n = 42), similar or higher proportions of facilities reported that they never referred smokers to onsite cessation services (68%; n = 42) or quitlines (77%; n = 47), provided cessation counseling (81%; n = 50), or recommended medications (85%; n = 52). CONCLUSIONS: In general, screening facilities are meeting CMS requirements for screening, but they are struggling to offer smoking cessation interventions other than providing self-help materials.

Timing and Outcomes of Tracheostomy Performed by Pulmonary and/or Critical Care Physicians.

BACKGROUND: Although pulmonary and/or critical care (P/CC) physicians perform percutaneous tracheostomy in mechanically ventilated patients, the trends, timing, and outcomes of this procedure have not been well described. This study aims to describe the trends, timing, and outcomes of this procedure. METHODS: Using 5% medicare data, we retrospectively examined a cohort who had tracheostomy performed after initiation of mechanical ventilation during acute hospitalization to describe the timing of tracheostomy placement by pulmonary and/or critical care (P/CC) physicians and associated outcomes. RESULTS: There were 4864 participants in the study cohort from 2007 to 2014. We examined the timing of tracheostomy (in days from initiation of mechanical ventilation), length of hospital stay, in-hospital death, and death within 30 days after hospital discharge. The percentage of tracheostomies performed by P/CC physicians increased significantly, from 7.2% in 2007 to 14.1% in 2014 (Cochran-Armitage test for trend, P = .001). Tracheostomies performed by P/CC physicians were more common in larger hospitals and major academic medical centers. After adjustment for baseline characteristics, the following parameters did not differ by provider: time to tracheostomy, length of hospital stay (days), in-hospital death, and death within 30 days after discharge. A tracheostomy was more likely to be performed by a P/CC physician at a larger (≥500 beds) hospital (adjusted odds ratio: 1.85, 95% confidence interval: 1.47-2.34). CONCLUSIONS: Tracheostomies are increasingly performed by P/CC physicians with similar outcomes, likely related to patient selection.

Trends in tobacco use and tobacco cessation counselling codes among Medicare beneficiaries, 2001-2014.

BACKGROUND: Analysis of Medicare data is often used to determine epidemiology, healthcare utilization and effectiveness of disease treatments. We were interested in whether Medicare data could be used to estimate prevalence of tobacco use. Currently, data regarding tobacco use is derived from Behavioral Risk Factor Surveillance System (BRFSS) survey data. We compare administrative claims data for tobacco diagnosis among Medicare beneficiaries to survey (BRFSS) estimates of tobacco use from 2001 to 2014. METHODS: Retrospective cross-sectional study comparing tobacco diagnoses using International Classification of Disease, Ninth Revision (ICD-9) codes for tobacco use in Medicare data to BRFSS data from 2001 to 2014 in adults age ≥ 65 years. Beneficiary data included age, gender, race, socioeconomic status, and comorbidities. Tobacco cessation counselling was also examined using Healthcare Common Procedure Coding System codes. RESULTS: The prevalence of Medicare enrollees aged ≥65 years who had a diagnosis of current tobacco use increased from 2.01% in 2001 to 4.8% in 2014, while the estimates of current tobacco use from BRFSS decreased somewhat (10.03% in 2001 vs. 8.77% in 2014). However, current tobacco use based on Medicare data remained well below the estimates from BRFSS. Use of tobacco cessation counselling increased over the study period with largest increases after 2010. CONCLUSIONS: The use of tobacco-related diagnosis codes increased from 2001 to 2014 in Medicare but still substantially underestimated the prevalence of tobacco use compared to BRFSS data.

A Closer Look-Who Are We Screening for Lung Cancer?

Objective: To evaluate the characteristics of individuals receiving lung cancer screening (LCS) and identify those with potentially limited benefit owing to coexisting chronic illnesses and/or comorbidities. Patients and Methods: In this retrospective study in the United States, patients were selected from a large clinical database who received LCS from January 1, 2019, through December 31, 2019, with at least 1 year of continuous enrollment. We assessed for potentially limited benefit in LCS defined strictly as not meeting the traditional risk factor inclusion criteria (age <55 years or >80 years, previous computed tomography scan within 11 months before an LCS examination, or a history of nonskin cancer) or liberally as having the potential exclusion criteria related to comorbid life-limiting conditions, such as cardiac and/or respiratory disease. Results: A total of 51,551 patients were analyzed. Overall, 8391 (16.3%) individuals experienced a potentially limited benefit from LCS. Among those who did not meet the strict traditional inclusion criteria, 317 (3.8%) were because of age, 2350 (28%) reported a history of nonskin malignancy, and 2211 (26.3%) underwent a previous computed tomography thorax within 11 months before an LCS examination. Of those with potentially limited benefit owing to comorbidity, 3680 (43.9%) were because of severe respiratory comorbidity (937 [25.5%] with any hospitalization for coronary obstructive pulmonary disease, interstitial lung disease, or respiratory failure; 131 [3.6%] with hospitalization for respiratory failure requiring mechanical ventilation; or 3197 [86.9%] with chronic obstructive disease/interstitial lung disease requiring outpatient oxygen) and 721 (8.59%) with cardiac comorbidity. Conclusion: Up to 1 of 6 low-dose computed tomography examinations may have limited benefit from LCS.

A protocol for a cluster randomized trial of care delivery models to improve the quality of smoking cessation and shared decision making for lung cancer screening.

BACKGROUND: Patients eligible for lung cancer screening (LCS) are those at high risk of lung cancer due to their smoking histories and age. While screening for LCS is effective in lowering lung cancer mortality, primary care providers are challenged to meet beneficiary eligibility for LCS from the Centers for Medicare & Medicaid Services, including a patient counseling and shared decision-making (SDM) visit with the use of patient decision aid(s) prior to screening. METHODS: We will use an effectiveness-implementation type I hybrid design to: 1) identify effective, scalable smoking cessation counseling and SDM interventions that are consistent with recommendations, can be delivered on the same platform, and are implemented in real-world clinical settings; 2) examine barriers and facilitators of implementing the two approaches to delivering smoking cessation and SDM for LCS; and 3) determine the economic implications of implementation by assessing the healthcare resources required to increase smoking cessation for the two approaches by delivering smoking cessation within the context of LCS. Providers from different healthcare organizations will be randomized to usual care (providers delivering smoking cessation and SDM on site) vs. centralized care (smoking cessation and SDM delivered remotely by trained counselors). The primary trial outcomes will include smoking abstinence at 12-weeks and knowledge about LCS measured at 1-week after baseline. CONCLUSION: This study will provide important new evidence about the effectiveness and feasibility of a novel care delivery model for addressing the leading cause of lung cancer deaths and supporting high-quality decisions about LCS. GOV PROTOCOL REGISTRATION: NCT04200534 TRIAL REGISTRATION: ClinicalTrials.govNCT04200534.

Characteristics and Factors Associated With Mortality in Patients With Coronavirus Disease 2019 and Pneumothorax.

Objective: To describe the incidence, clinical characteristics, and factors associated with mortality in patients hospitalized for coronavirus disease 2019 (COVID-19) in whom pneumothorax developed. Patients and Methods: This study was a retrospective analysis conducted using a large administrative database of adult patients hospitalized for COVID-19 in the United States from February 1, 2020, to June 10, 2021. We characterized the clinical features of patients in whom pneumothorax developed and the factors associated with mortality and stratified pneumothorax by the timing of the initiation of invasive mechanical ventilation (IMV) and by the time of hospital admission (early versus late). Results: A total of 811,065 adult patients had a positive test result for severe acute respiratory syndrome coronavirus 2, of whom 103,858 (12.8%) were hospitalized. Pneumothorax occurred in 1915 patients (0.24% overall and 1.84% among hospitalized patients). Over time, the use of steroids and remdesivir increased, whereas the use of IMV, pneumothorax rates, and mortality decreased. The clinical characteristics associated with pneumothorax were male sex; the receipt of IMV; and treatment with steroids, remdesivir, or convalescent plasma. Most patients with pneumothorax received IMV, but pneumothorax developed before the initiation of IMV and/or early during hospitalization in majority. Multivariable analysis revealed that pneumothorax increased the risk of death (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.06-1.24). In patients who did not receive IMV, pneumothorax led to nearly twice the mortality (aHR, 1.99; 95% CI, 1.56-2.54). Increased mortality was also noted when pneumothorax occurred before IMV (aHR, 1.37; 95% CI, 1.11-1.69) and within 7 days of hospital admission (aHR, 1.60; 95% CI, 1.29-1.98). Conclusion: The overall incidence of pneumothorax in patients hospitalized for COVID-19 was low. Pneumothorax is an independent risk factor for death.

Impact of the shared decision-making process on lung cancer screening decisions.

BACKGROUND: Professional organizations recommend the use of shared decision-making (SDM) in supporting patients' decisions about lung cancer screening (LCS). The objective of this study was to assess the impact of the SDM process on patient knowledge about LCS, decisional conflict, intentions to adhere to screening recommendations, and its role in how the patient made the final decision. METHODS: This study surveyed patients screened for lung cancer within 12 months of the survey, recruited from two academic tertiary care centers in the South Central Region of the U.S. (May to July 2018). RESULTS: Two hundred and sixty-four patients completed the survey (87.9% White, 52% male, and mean age of 64.81). Higher SDM process scores (which indicates a better SDM process reported by patients) were significantly associated with greater knowledge of LCS (b = 0.17 p < 0.01). Higher SDM process scores were associated with less decisional conflict about their screening choice (b = 0.45, p < 0.001), greater intentions to make the same decision again (OR = 1.42, 95% CI = [1.06-1.89]), and greater intentions to undergo LCS again (OR = 1.32, 95% CI = [1.08-1.62]). The SDM process score was not associated with patients' report of whether or not they shared the final decision with the healthcare provider (OR = 1.07, 95% CI = [0.85-1.35]). CONCLUSION(S): This study found that a better SDM process was associated with better affective-cognitive outcomes among patients screened for lung cancer.

Ice Capades: Skating Around Current Practice of Cryobiopsy for ILD.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) has been proposed as a potentially safer alternative in the diagnosis of interstitial lung disease. The current practice of TBLC is unknown as most published data come from case reports, case series, and a few trials. The authors report the practice patterns of TBLC on the basis of survey responses. METHODS: The authors created an anonymous online survey to assess how proceduralists evaluate patients, perform, and manage complications of TBLC. Surveys were distributed through social media and e-mail distribution lists from the American Association of Bronchology and Interventional Pulmonology and the Society of Advanced Bronchoscopists. Aggregated responses are reported as counts, percentages, and averages. RESULTS: Surveys show significant variation in parameters providers use to assess appropriate patients for procedures, how specific aspects of TBLC are performed, and how complications and results are managed. CONCLUSION: This is the first and largest survey of providers describing the current large variation in the use of cryobiopsy for the evaluation of interstitial lung disease. The standardized practice is essential to understand the true diagnostic accuracy or rate of complications related to TBLC.

Determining Cause of Death During Coronavirus Disease 2019 Pandemic.

Controversy exists whether the cause of death due to severe acute respiratory syndrome coronavirus 2 is directly related to the infection or to underlying conditions. The purpose of this study is to assess the relationship of severe acute respiratory syndrome coronavirus 2 infection with the cause of death in hospitalized patients. DESIGN: Retrospective observational study; deidentified discharge summaries of deceased patients were reviewed by two intensivists and classified as coronavirus disease 2019-related (caused by severe acute respiratory syndrome coronavirus 2) or coronavirus disease 2019-unrelated (not caused by severe acute respiratory syndrome coronavirus 2 or indeterminate) deaths. For classification disagreement, a separate group of three intensivists reviewed the discharge summaries and arbitrated to determine the cause of death. SETTING: Single-center study performed at the University of Texas Medical Branch. PATIENTS: All adult patients (> 18 yr) admitted from March 10, 2020, to October 22, 2020, with positive severe acute respiratory syndrome coronavirus 2 test results who expired during their hospitalization were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, comorbidities, prescribed medications, and ventilatory support data were collected. Comparison between groups was performed using t test and chi-square test. During the study period, 1,052 patients were admitted within 14 days of severe acute respiratory syndrome coronavirus 2-positive test results, of whom 100 expired during the hospitalization. Deceased patients were predominantly male and older than 65 years. Obesity (body mass index ≥ 30 kg/m2) was present in 41%, and common comorbidities included hypertension (47%), diabetes (30%), and heart failure (20%). Death was classified as directly caused by severe acute respiratory syndrome coronavirus 2 in 85% and not caused by severe acute respiratory syndrome coronavirus 2 in 5%. An indeterminate cause of death in 10% was due to insufficient information or an atypical presentation. The observed interrater agreement on the cause of death classification was 81%. CONCLUSIONS: In this single-center study, the majority of deaths in severe acute respiratory syndrome coronavirus 2-positive hospitalized patients were related to a typical or atypical presentation of coronavirus disease 2019 disease.

Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019.

RATIONALE: There is controversy concerning the association of chronic obstructive pulmonary disease (COPD) as an independent risk factor for mortality in patients hospitalized with Coronavirus Disease 2019 (COVID-19). We hypothesize that patients with COPD hospitalized for COVID-19 have increased mortality risk. OBJECTIVE: To assess whether COPD increased the risk of mortality among patients hospitalized for COVID-19. METHODS: We conducted a retrospective cohort analysis of patients with COVID-19 between February 10, 2020, and November 10, 2020, and hospitalized within 14 days of diagnosis. Electronic health records from U.S. facilities (Optum COVID-19 data) were used. RESULTS: In our cohort of 31,526 patients, 3030 (9.6%) died during hospitalization. Mortality in patients with COPD was higher than that of patients without COPD, 14.02% and 8.8%, respectively. Univariate (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.54 to 1.84) and multivariate (OR 1.33; 95% CI 1.18 to 1.50) analysis showed that patients with COPD had greater odds of death due to COVID-19 than patients without COPD. We found significant interactions between COPD and sex and COPD and age. Specifically, the increased mortality risk associated with COPD was observed among female (OR 1.62; 95% CI 1.36 to 1.95) but not male patients (OR 1.14; 95% CI 0.97 to 1.34); and in patients aged 40 to 64 (OR 1.42; 95% CI 1.07 to 1.90) and 65 to 79 (OR 1.48; 95% CI 1.23 to 1.78) years. CONCLUSIONS: COPD is an independent risk factor for death in adults aged 40 to 79 years hospitalized with COVID-19 infection.

Shared Decision-Making for Lung Cancer Screening: How Well Are We "Sharing"?

BACKGROUND: Lung cancer screening (LCS) reduces lung cancer mortality, but it also carries a range of risks. Shared decision-making (SDM) is a process of engaging patients in their health care decisions and is a vital component of LCS. RESEARCH QUESTION: What is the quality of SDM among patients recently assessed for LCS? STUDY DESIGN AND METHODS: Cross-sectional study of screened patients recruited from two academic tertiary care centers in the South Central Region of the United States. Self-reported surveys assessed patient demographics, values related to outcomes of LCS, knowledge, SDM components including receipt of educational materials, and decisional conflict. RESULTS: Recently screened patients (n = 266) possessed varied LCS knowledge, answering an average of 41.4% of questions correctly. Patients valued finding cancer early over concerns about harms. Patients indicated that LCS benefits were presented to them by a health care provider far more often than harms (68.3% vs 20.8%, respectively), and 30.7% reported they received educational materials about LCS during the screening process. One-third of patients had some decisional conflict (33.6%) related to their screening decisions, whereas most patients (86.6%) noted that they were involved in the screening decision as much as they wanted. In multivariate models, non-White race and having less education were related to lower knowledge scores. Non-White patients and former smokers were more likely to be conflicted about the screening decision. Most patients (n = 227 [85.3%]) indicated that a health care provider had discussed smoking cessation or abstinence with them. INTERPRETATION: Among recently screened patients, the quality of decision-making about LCS is highly variable. The low use of educational materials including decision aids and imbalance of conveying benefit vs risk information to patients is concerning. A structured approach using decision aids may assist with providing a balanced presentation of information and may improve the quality of SDM.

Smoking cessation and shared decision-making practices about lung cancer screening among primary care providers.

OBJECTIVE: We describe primary care providers' current practice patterns related to smoking cessation counseling and lung cancer screening (LCS). METHODS: Family, internal medicine, and pulmonary medicine providers from two medical centers were asked to complete an electronic survey to report their practice patterns. RESULTS: Of 52 participating providers, most reported initiating three major components of a smoking cessation intervention often or very often: advise to quit (50, 96%), assess willingness to quit (47, 90%), and assist with counseling or pharmacotherapy (49, 94%). However, other components were less commonly initiated such as arranging follow-ups (only 11 providers indicated recommending them often or very often, 21%) and less than half of providers reported that they often or very often recommend cessation counseling or pharmacotherapy of any type (except varenicline), though family medicine providers were more likely to recommend pharmacotherapy compared to the other specialists (p < 0.01). The majority of providers (47, 92%) reported that they engage in informed/shared decision-making about LCS, although only about one-third (17, 33%) indicated using a patient decision aid. Pulmonary medicine providers were more likely to use decision aids than providers from internal or family medicine (p < 0.04). CONCLUSIONS: Within the context of LCS, primary care providers report often having conversations about smoking cessation with their patients who smoke, have no clear preference for type of treatment, and rarely use follow-up calls or visits pertaining to quitting smoking. While many providers report engaging in shared decision-making about LCS, few use a decision aid for this conversation.

Use of Imaging and Diagnostic Procedures After Low-Dose CT Screening for Lung Cancer.

BACKGROUND: Clinical trials have demonstrated a mortality benefit from lung cancer screening by low-dose CT (LDCT) in current or past tobacco smokers who meet criteria. Potential harms of screening mostly relate to downstream evaluation of abnormal screens. Few data exist on the rates outside of clinical trials of imaging and diagnostic procedures following screening LDCT. We describe rates in the community setting of follow-up imaging and diagnostic procedures after screening LDCT. METHODS: We used Clinformatics Data Mart national database to identify enrollees age 55 to 80 year who underwent screening LDCT from January 1, 2016, to December 31, 2016. We assessed rates of follow-up imaging (diagnostic chest CT scan, MRI, and PET) and follow-up procedures (bronchoscopy, percutaneous biopsy, thoracotomy, mediastinoscopy, and thoracoscopy) in the 12 months following LDCT for lung cancer screening. We also assessed these rates in an age-, sex-, and number of comorbidities-matched population that did not undergo LDCT to estimate rates unrelated to the screening LDCT. We then reported the adjusted rate of follow-up testing as the observed rate in the screening LDCT population minus the rate in the non-LDCT population. RESULTS: Among 11,520 enrollees aged 55 to 80 years who underwent LDCT in 2016, the adjusted rates of follow up 12 months after LDCT examinations were low (17.7% for imaging and 3.1% for procedures). Among procedures, the adjusted rates were 2.0% for bronchoscopy, 1.3% for percutaneous biopsy, 0.9% for thoracoscopy, 0.2% for mediastinoscopy, and 0.4% for thoracotomy. Adjusted rates of follow-up procedures were higher in enrollees undergoing an initial screening LDCT (3.3%) than in those after a second screening examination (2.2%). CONCLUSIONS: In general, imaging and rates of procedures after screening LDCT was low in this commercially insured population.

Reliability of self-reported smoking history and its implications for lung cancer screening.

Clinical guidelines endorse either a 30 or 20 pack-year smoking history threshold when determining eligibility for lung cancer screening (LCS). However, self-reported smoking history is subject to recall bias that can affect patient eligibility. We examined the reliability of smokers' self-reported tobacco use and its impact on eligibility for LCS. Current or former smokers aged 55-77 years completed questionnaires requesting demographic information and smoking history. Data were collected between December 2014 and September 2015. Total pack-year smoking history was calculated for each participant based on their responses at baseline and one month later. One hundred and two participants completed the study (mean age = 63.6 years). The intraclass correlation coefficient for the pack-year estimate was 0.93. For the 30 pack-year threshold, eight (7.8%) participants were eligible at one but not both assessment periods. For the 20 pack-year threshold, twelve participants (11.8%) were eligible at one but not both assessment periods. Inconsistent reporting was higher among current compared to former smokers. Smokers' self-reported tobacco use appears highly reliable over short time periods. Nevertheless, there is some inconsistent reporting. We recommend that clinicians carefully assess smoking history, probe patients' recall of duration and quantity of smoking, and collect tobacco use information at every encounter.

Pattern and Adherence to Maintenance Medication Use in Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease: 2008-2013.

Background: Maintenance medications provide symptomatic relief, improve lung function and reduce the risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Despite their proven benefits, limited information exists on maintenance medication use and adherence among users. Objective: We examined the patterns and factors associated with the receipt of and adherence to maintenance medication in individuals with COPD. Methods: A retrospective cross-sectional study of 5% of Medicare beneficiaries enrolled in Parts A, B and D with COPD who received maintenance medication from 2008 to 2013 was conducted. Maintenance medication includes: inhaled corticosteroids (ICSs), long-acting beta2- agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) alone or in combination. We examined the proportion of beneficiaries with COPD who had at least one prescription filled for maintenance medication. Among users of maintenance medications, we also examined adherence, defined as proportion of days covered (PDC) ≥80% over the year from the first maintenance medication prescription fill date. Results: Overall, maintenance medication (LAMAs, LABAs, ICSs and/or LABA/ICS) use increased from 67.8% in 2008 to 72.1% in 2013. The increase is related to increases in use of LABA/ICS, which rose from 41.1% in 2008 to 49.6% in 2013. Factors associated with receipt of maintenance medication include female gender, recent COPD hospitalization (odds ratio [OR] 1.63; 95% confidence interval [CI] 1.54-1.73), oxygen therapy (OR 1.74 95% CI, 1.68-1.81), dual eligibility status (OR 1.45; 95% CI 1.39-1.51), higher education level and evaluation by a pulmonary provider (OR 1.88; 95% CI 1.81-1.96). The overall adherence among maintenance medication users remained flat. The most important factor associated with adherence was dual eligibility status (OR, 1.67; 95% CI: 1.59-1.75). Conclusions: Receipt of maintenance medications increased during the study period and was higher in those with dual eligibility. Overall, adherence to maintenance medications was suboptimal and remained unchanged.

Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat.

BACKGROUND: Both statins and thiazolidinediones have antiinflammatory properties. However, the exact mechanisms underlying these effects are unknown. We investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the myocardial content of lipoxin-A4 and 15(R)-epi-lipoxin-A4 (15-epi-LXA4), both arachidonic acid products with strong antiinflammatory properties. METHODS AND RESULTS: In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5, or 10 mg x kg(-1) x d(-1); ATV 2, 5, or 10 mg x kg(-1) x d(-1); or PIO 10 mg x kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1). In experiment 2, rats received water; PIO 10 mg x kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1); PIO+ATV and valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor; PIO+ATV and zileuton, a selective 5-lipoxygenase inhibitor; or zileuton alone. There were 4 rats in each group. Hearts were harvested and analyzed for myocardial lipoxin-A4 and 15-epi-LXA4 levels and for COX-2 and 5-lipoxygenase protein expression. ATV and PIO at 5 and 10 mg x kg(-1) . d(-1) significantly increased myocardial 15-epi-LXA4 levels compared with the sham-treated group (0.51 +/- 0.02 ng/mg). Myocardial 15-epi-LXA4 were significantly higher in the PIO+ATV group (1.29 +/- 0.02 ng/mg; P < 0.001 versus each other group). Both valdecoxib and zileuton abrogated the PIO+ATV increase in 15-epi-LXA4, whereas zileuton alone had no effect. PIO, ATV, and their combination resulted in a small increase in myocardial lipoxin-A4 levels, which was not statistically significant. ATV alone or in combination with PIO markedly augmented COX-2 expression. PIO had a much smaller effect on COX-2 expression. Myocardial expression of 5-lipoxygenase was not altered by PIO, ATV, or their combination. CONCLUSIONS: Both PIO and ATV increase myocardial levels of 15-epi-LXA4, a mediator with antiinflammatory properties. This finding may explain the antiinflammatory properties of both PIO and ATV.

Activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) by atorvastatin is mediated by 15-deoxy-delta-12,14-PGJ2.

Several studies suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) activate peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Atorvastatin (ATV) increases myocardial levels of prostaglandins (PG) by upregulating and activating cytosolic-phospholipase-A(2) and cycloxygenase-2 (COX2). We investigated whether ATV activates PPAR-gamma via 15-deoxy-delta-12,14-PGJ(2) (15DPGJ(2)) an endogenous ligand of PPAR-gamma and a product of PGD(2), and to compare the effects of pioglitazone (PIO), a known direct PPAR-gamma activator, to that of ATV. First we measured myocardial 15DPGJ(2) levels in the rat heart after a 3-day pretreatment with oral ATV (10 mg/(kg d)), PIO (10 mg/(kg d)), ATV+PIO, ATV+COX1 inhibitor, and ATV+COX2 inhibitor. We also assessed in human umbilical venous endothelial cells (HUVEC) whether ATV and PIO activate PPAR-gamma via 15DPGJ(2) using siRNA targeted to PGD(2) synthase. Both 15DPGJ(2) levels and PPAR-gamma activation were assessed. ATV and PIO increased myocardial 15DPGJ(2) levels in the rat myocardium and HUVEC. siRNA inhibited this increase in both groups. Both ATV and PIO augmented PPAR-gamma activation while co-treatment with siRNA completely blocked the ATV effect but only partially inhibited the PIO effect. In conclusion, both ATV and PIO activate PPAR-gamma and increase myocardial 15DPGJ(2) levels. Activation of PPAR-gamma by ATV is mediated solely by 15DPGJ(2), whereas PIO activates PPAR-gamma both directly and indirectly via 15DPGJ(2).

Symptomatic Patent Foramen Ovale with Hemidiaphragm Paralysis.

Dyspnea accounts for more than one-fourth of the hospital admissions from Emergency Department. Chronic conditions such as Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and Asthma are being common etiologies. Less common etiologies include conditions such as valvular heart disease, pulmonary embolism, and right-to-left shunt (RLS) from patent foramen ovale (PFO). PFO is present in estimated 20-30% of the population, mostly a benign condition. RLS via PFO usually occurs when right atrium pressure exceeds left atrium pressure. RLS can also occur in absence of higher right atrium pressure. We report one such case that highlights the importance of high clinical suspicion, thorough evaluation, and percutaneous closure of the PFO leading to significant improvement in the symptoms.

Mixing It Up: Coadministration of tPA/DNase in Complicated Parapneumonic Pleural Effusions and Empyema.

BACKGROUND: A recent randomized controlled trial showed 12 serial doses of tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) is safe and effective in managing complicated parapneumonic pleural effusions and empyema (CPEE). However, this regimen is laborious, requiring trained personnel to open/close the chest tube 8 times daily for 3 days. We present our observational data using a simplified regimen of coadministered tPA/DNase. MATERIALS AND METHODS: This is a retrospective observational study of patients who received coadministered tPA/DNase for CPEE from January 2012 to April 2015 at the University of Texas Medical Branch. Patient demographics, pleural fluid, radiologic and treatment characteristics, and outcomes were collected. Data are presented as proportions and percentages. Our primary outcome was successful treatment without need of surgery and discharge home alive. Secondary outcomes were dose and length of treatment and hospital stay, treatment complications, and 90-day mortality. RESULTS: The study included 39 patients. All pleural effusions were loculated, 59% macroscopically purulent, 50% had a positive organism in Gram stain, and 40% were culture positive. A median of 6 (interquartile range, 3.5 to 6) doses were coadministered mainly via small bore chest tube (≤14 Fr in 79%) with a median of 14.5 (interquartile range, 9.5 to 21.5) hospital days. Overall, 85% were successfully treated without need for surgery. Treatment failures occurred in 15%: 3/39 (7%) received surgery; 3/39 (7%) died. Only 1 (2.5%) complication of hemorrhagic pleural effusion resolved after discontinuation of intrapleural treatment. CONCLUSIONS: Our study shows intrapleural coadministration of tPA/DNase was effective and safe in management of CPEE.