Peer Texting to Promote Quitline Use and Smoking Cessation Among Rural Participants in Vietnam: Randomized Clinical Trial.

Objectives: We tested an adapted version of an effective U.S.-based peer-texting intervention to promote Quitline use and smoking cessation among rural participants in Vietnam. Methods: We conducted a two-arm randomized trial with participants recruited at four rural community centers. The intervention included peer messages sent for six months that promoted Quitline use and smoking cessation. Additionally, biweekly two-way text messages assessed participants' interest in Quitline referral and current smoking status. Comparison participants received only the bi-weekly text message assessment of their current smoking status. At six months, we assessed Quitline use and smoking cessation. Smoking cessation was assessed using the 7-day point prevalence question and verified with a carbon monoxide breath monitor (<=6 ppm). Results: Among 750 participants, the intervention had higher Quitline verified use (18%, 95% CI 0.14, 0.22) than comparison (1%, 95% CI .2, 2, p < 0.0001). Carbon-monoxide-verified smoking cessation did not differ between the two groups. However, intervention (28.3%, 95% CI) and comparison (28.1%, 95% CI) participants had substantial rates of carbon monoxide cessation at 6 months (both 28%). Conclusion: Our study highlighted the promise of texting interventions to extend tobacco control efforts in Vietnam.

Telemedicine-based inspiratory muscle training and walking promotion with lung cancer survivors following curative intent therapy: a parallel-group pilot randomized trial.

PURPOSE: Following curative-intent therapy of lung cancer, many survivors experience dyspnea and physical inactivity. We investigated the feasibility, acceptability, safety, and potential efficacy of inspiratory muscle training (IMT) and walking promotion to disrupt a postulated "dyspnea-inactivity" spiral. METHODS: Between January and December 2022, we recruited lung cancer survivors from Kaiser Permanente Colorado who completed curative-intent therapy within 1-6 months into a phase-IIb, parallel-group, pilot randomized trial (1:1 allocation). The 12-week intervention, delivered via telemedicine, consisted of exercise training (IMT + walking), education, and behavior change support. Control participants received educational materials on general exercise. We determined feasibility a priori: enrollment of ≥ 20% eligible patients, ≥ 75% retention, study measure completion, and adherence. We assessed acceptability using the Telemedicine-Satisfaction-and-Usefulness-Questionnaire and safety events that included emergency department visits or hospitalizations. Patient-centered outcome measures (PCOMs) included dyspnea (University-of-California-San-Diego-Shortness-of-Breath-Questionnaire), physical activity (activPAL™ steps/day), functional exercise capacity (mobile-based-six-minute-walk-test), and health-related quality of life (HRQL, St.-George's-Respiratory-Questionnaire). We used linear mixed-effects models to assess potential efficacy. RESULTS: We screened 751 patients, identified 124 eligible, and consented 31 (25%) participants. Among 28 participants randomized (14/group), 22 (11/group) completed the study (79% retention). Intervention participants returned > 90% of self-reported activity logs, completed > 90% of PCOMs, and attended > 90% of tele-visits; 75% of participants performed IMT at the recommended dose. Participants had high satisfaction with tele-visits and found the intervention useful. There was no statistically significant difference in safety events between groups. Compared to control participants from baseline to follow-up, intervention participants had statistically significant and clinically meaningful improved HRQL (SGRQ total, symptom, and impact scores) (standardized effect size: -1.03 to -1.30). CONCLUSIONS: Among lung cancer survivors following curative-intent therapy, telemedicine-based IMT + walking was feasible, acceptable, safe, and had potential to disrupt the "dyspnea-inactivity" spiral. Future efficacy/effectiveness trials are warranted and should incorporate IMT and walking promotion to improve HRQL. TRIAL REGISTRATION: ClinicalTrials.gov NCT05059132.

Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment.

Introduction: Iloprost, a prostacyclin analog, has lung cancerpreventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable. We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance. Methods: Participants self-administered nebulized iloprost (5ug) or placebo four (QID) or two (BID) times daily. As QID dose was well tolerated and due to expiration of the placebo, the BID dosing and placebo were eliminated early on in the trial. Bronchoscopy with biopsyat six standard sites was performed at treatment initiation and two months post-iloprost, with exploratory histological analysis. Bulk RNA sequencing, single cell RNA sequencing and an in vitro assay of epithelial progenitor cell iloprost response were performed on a subset of biopsies in an exploratory investigation of response mechanisms and predictive biomarkers. Results and discussion: Thirty-four of a planned 48 participants were recruited to the trial.Inhaled iloprost was well tolerated with no adverse events > grade 2. Compliance was 67% in the QID group. The trial was not powered to detect histologic response and none was found. Bulk RNA sequencing of biopsies pre/post iloprost suggest that iloprost is immunomodulatory and downregulates cell proliferation pathways. Single cell RNA sequencing showed an increase in CD8-positive T cells with upregulation of genes in interferon γ signaling. In vitro iloprost response by epithelial progenitor cells correlated with histologic response with kappa coefficient of 0.81 (95% CI 0.47, 1.0). Inhaled iloprost was well tolerated with suboptimal compliance. Molecular analysis suggested that iloprosthas immunomodulatory and antiproliferative effects.The progenitor cell iloprost response assay may be a promising avenue to develop predictive biomarkers. Clinical trial registration: https://clinicaltrials.gov/study/NCT02237183, identifier NCT02237183.

Lung cancer survivors' views on telerehabilitation following curative intent therapy: a formative qualitative study.

OBJECTIVES: To inform personalised home-based rehabilitation interventions, we sought to gain in-depth understanding of lung cancer survivors' (1) attitudes and perceived self-efficacy towards telemedicine; (2) knowledge of the benefits of rehabilitation and exercise training; (3) perceived facilitators and preferences for telerehabilitation; and (4) health goals following curative intent therapy. DESIGN: We conducted semi-structured interviews guided by Bandura's Social Cognitive Theory and used directed content analysis to identify salient themes. SETTING: One USA Veterans Affairs Medical Center. PARTICIPANTS: We enrolled 20 stage I-IIIA lung cancer survivors who completed curative intent therapy in the prior 1-6 months. Eighty-five percent of participants had prior experience with telemedicine, but none with telerehabilitation or rehabilitation for lung cancer. RESULTS: Participants viewed telemedicine as convenient, however impersonal and technologically challenging, with most reporting low self-efficacy in their ability to use technology. Most reported little to no knowledge of the potential benefits of specific exercise training regimens, including those directed towards reducing dyspnoea, fatigue or falls. If they were to design their own telerehabilitation programme, participants had a predominant preference for live and one-on-one interaction with a therapist, to enhance therapeutic relationship and ensure correct learning of the training techniques. Most participants had trouble stating their explicit health goals, with many having questions or concerns about their lung cancer status. Some wanted better control of symptoms and functional challenges or engage in healthful behaviours. CONCLUSIONS: Features of telerehabilitation interventions for lung cancer survivors following curative intent therapy may need to include strategies to improve self-efficacy and skills with telemedicine. Education to improve knowledge of the benefits of rehabilitation and exercise training, with alignment to patient-formulated goals, may increase uptake. Exercise training with live and one-on-one therapist interaction may enhance learning, adherence, and completion. Future work should determine how to incorporate these features into telerehabilitation.

Cancer-related Fatigue in Lung Cancer: A Research Agenda: An Official American Thoracic Society Research Statement.

Background: Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. Objectives: 1) To identify and prioritize knowledge and research gaps and 2) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. Methods: We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. Results: This statement identifies knowledge gaps in the 1) detection and diagnostic evaluation of CRF in lung cancer survivors; 2) timing, goals, and implementation of physical activity and rehabilitation; and 3) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. Conclusions: This statement offers a prioritized research agenda to 1) advance clinical and research efforts and 2) increase awareness of CRF in lung cancer survivors.

Fabrication of Porous Fe-Based Metal-Organic Complex for the Enhanced Delivery of 5-Fluorouracil in In Vitro Treatment of Cancer Cells.

Metal-organic complexes are one of the most studied materials in the last few decades, which are fabricated from organic ligands and metal ions to form robust frameworks with porous structures. In this work, iron-1,4-benzenedicarboxylic-polyethylene glycol (Fe-BDC-PEG) with a porous structure was successfully constructed by an iron(III) benzene dicarboxylate and polyethylene glycol diacid. The drug-delivery properties of the resultant Fe-BDC-PEG were tested for the loading and release of the 5-fluorouracil compound. The maximal loading capacity of Fe-BDC-PEG for 5-fluorouracil was determined to be 348.22 mg/g. The drug release of 5-fluorouracil-loaded Fe-BDC-PEG after 7 days was 92.69% and reached a maximum of 97.52% after 10 days. The 7 day and acute oral toxicity of Fe-BDC-PEG in mice were studied. The results show that no reasonable change or mortality was observed upon administration of Fe-BDC-PEG complex in mice at 10 g/kg body weight. When the uptake of Fe-BDC-PEG particles in mice was continued for 7 consecutive days, the mortality, feed consumption, body weight, and daily activity were negligibly changed.

Modulation of osmoprotection and antioxidant defense by exogenously applied acetate enhances cadmium stress tolerance in lentil seedlings.

To examine the potential role of acetate in conferring cadmium (Cd) stress tolerance in lentil (Lens culinaris), several phenotypical and physio-biochemical properties have been examined in Cd-stressed lentil seedlings following acetate applications. Acetate treatment inhibited the translocation of Cd from roots to shoots, which resulted in a minimal reduction in photosynthetic pigment contents. Additionally, acetate-treated lentil showed higher shoot (1.1 and 11.72%) and root (4.98 and 30.64%) dry weights compared with acetate-non-treated plants under low-Cd and high-Cd concentrations, respectively. Concurrently, acetate treatments increase osmoprotection under low-Cd stress through proline accumulation (24.69%), as well as enhancement of antioxidant defense by increasing ascorbic acid content (239.13%) and catalase activity (148.51%) under high-Cd stress. Acetate-induced antioxidant defense resulted in a significant diminution in hydrogen peroxide, malondialdehyde and electrolyte leakage in Cd-stressed lentil seedlings. Our results indicated that acetate application mitigated oxidative stress-induced damage by modulating antioxidant defense and osmoprotection, and reducing root-to-shoot Cd transport. These findings indicate an important contribution of acetate in mitigating the Cd toxicity during growth and development of lentil seedlings, and suggest that the exogenous applications of acetate could be an economical and new avenue for controlling heavy metal-caused damage in lentil, and potentially in many other crops.

Modifiable factors associated with health-related quality of life among lung cancer survivors following curative intent therapy.

OBJECTIVE: The number of lung cancer survivors is increasing along with advances in screening, diagnosis, and treatment. Following curative intent therapy, many lung cancer survivors experience significant health-related quality of life (HRQL) impairments. We sought to identify potentially modifiable factors that contribute to the HRQL of these patients. MATERIALS AND METHODS: In this cross-sectional observational study of disease-free, stage I-IIIA lung cancer survivors following curative intent therapy, we used a conceptual model to examine factors that included behavioral, objective functional and physiologic, self-rated function and symptom burden, specific comorbidities, and non-modifiable demographic and clinical lung cancer-related characteristics. We assessed HRQL using the valid and prognostic European Organization for Research and Treatment of Cancer Quality of Life (QoL) Core 30 global health/QoL subscale. We used univariable and multivariable linear regression modeling with backward elimination of potentially modifiable and non-modifiable factors, and interpreted clinically and statistically significant, consistent, and independent modifiable factors as meaningful. RESULTS: Among 75 participants at a median of 12 months since treatment completion, the mean (standard deviation) C30 global health/QoL score was 62.7 (23.3) points (0-100 scale range). In multivariable analysis, with and without non-modifiable factors, we identified three clinically and statistically significant, consistent, and independent factors (unstandardized ß range) associated with global health/QoL: 1) abnormal exercise-induced dyspnea (-9.23 to -10.0 points); 2) impaired self-rated role function (or inability to perform work or daily activities and pursuing leisure-time activities) (-12.6 to -16.4 points); and 3) abnormal insomnia (or trouble sleeping) (-12.6 to -16.4 points). CONCLUSION: We identified meaningful modifiable factors associated with the HRQL of disease-free, stage I-IIIA lung cancer survivors following curative intent therapy. Interventions to improve the HRQL of these patients should aim to reduce exercise-induced dyspnea, improve role function - the ability to perform work and other daily including leisure-time activities, and control insomnia.

Ultrasonic-Assisted Synthesis of Fe-BTC-PEG Metal-Organic Complex: An Effective and Safety Nanocarrier for Anticancer Drug Delivery.

The porous metal-organic complexes are emerging as novel carriers for effective and safe delivery of drugs for cancer treatment, minimizing the side effect of drug overuse during cancer treatment. This study fabricated the Fe-BTC-PEG metal-organic complex from Fe ions, trimesic acid, and poly(ethylene glycol) as precursors using an ultrasonic-assisted method. The morphology and crystallinity of the resultant complex were observed by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. FTIR spectroscopy was employed to investigate the functional groups on the surface of the Fe-BTC-PEG complex. The result showed that the prepared Fe-BTC-PEG complex was in particle form with low crystallinity and diameter ranging from 100 to 200 nm. The obtained Fe-BTC-PEG complex exhibited a high loading capacity for the 5-fluorouracil (5-FU) anticancer drug with a maximal capacity of 364 mg/g. The releasing behavior of 5-fluorouracil from the 5-FU-loaded Fe-BTC-PEG complex was studied. Notably, the acute oral toxicity of the Fe-BTC-PEG metal-organic complex was also carried out to evaluate the safety of the material in practical application.

mHealth Messaging to Motivate Quitline Use and Quitting: Protocol for a Community-Based Randomized Controlled Trial in Rural Vietnam.

BACKGROUND: Tobacco kills more than 8 million people each year, mostly in low- and middle-income countries. In Vietnam, 1 in every 2 male adults smokes tobacco. Vietnam has set up telephone Quitline counseling that is available to all smokers, but it is underused. We previously developed an automated and effective motivational text messaging system to support smoking cessation among US smokers. OBJECTIVE: The aim of this study is to adapt the aforementioned system for rural Vietnamese smokers to promote cessation of tobacco use, both directly and by increasing the use of telephone Quitline counseling services and nicotine replacement therapy. Moreover, we seek to enhance research and health service capacity in Vietnam. METHODS: We are testing the effectiveness of our culturally adapted motivational text messaging system by using a community-based randomized controlled trial design (N=600). Participants were randomly allocated to the intervention (regular motivational and assessment text messages) or control condition (assessment text messages only) for a period of 6 months. Trial recruitment took place in four communes in the Hung Yen province in the Red River Delta region of Vietnam. Recruitment events were advertised to the local community, facilitated by community health workers, and occurred in the commune health center. We are assessing the impact of the texting system on 6-month self-reported and biochemically verified smoking cessation, as well as smoking self-efficacy, uptake of the Quitline, and use of nicotine replacement therapy. In addition to conducting the trial, the research team also provided ongoing training and consultation with the Quitline during the study period. RESULTS: Site preparation, staff training, intervention adaptation, participant recruitment, and baseline data collection were completed. The study was funded in August 2017; it was reviewed and approved by the University of Massachusetts Medical School Institutional Review Board in 2017. Recruitment began in November 2018. A total of 750 participants were recruited from four communes, and 700 (93.3%) participants completed follow-up by March 2021. An analysis of the trial results is in progress; results are expected to be published in late 2022. CONCLUSIONS: This study examines the effectiveness of mobile health interventions for smoking in rural areas in low- and middle-income countries, which can be implemented nationwide if proven effective. In addition, it also facilitates significant collaboration and capacity building among a variety of international partners, including researchers, policy makers, Quitline counselors, and community health workers. TRIAL REGISTRATION: ClinicalTrials.gov NCT03567993; https://clinicaltrials.gov/ct2/show/NCT03567993. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30947.

Association of Leisure-Time Physical Activity With Health-Related Quality of Life Among US Lung Cancer Survivors.

Background: Physical activity and exercise improve function, symptom control, and health-related quality of life (QoL) for many cancer survivors; however, the evidence is limited and inconsistent in lung cancer. We examined the relationship between leisure-time physical activity (LTPA) and health-related QoL in a national sample of US lung cancer survivors. Methods: We conducted a cross-sectional study using the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. We defined LTPA as a self-report of engaging in any physical activity or exercise such as running, calisthenics, golf, gardening, or walking for exercise in the past 30 days, health-related QoL as the number of days of having poor physical or mental health in the past 30 days, and general health status. We analyzed using multivariable logistic regressions with 95% confidence intervals (CIs). Results: Among 614 lung cancer survivors, 316 (51.5%) reported engaging in LTPA. The counts (and proportions) of participants who engaged in LTPA vs no LTPA were, respectively, 135 (42.7%) vs 63 (21.1%) for 0 days of poor physical health, 222 (70.3%) vs 174 (58.4%) for 0 days of poor mental health, and 158 (50.0%) vs 77 (25.8%) for good to excellent general health. In multivariable analyses, participating in LTPA was associated with odds ratios of 2.64 (95% CI = 1.76 to 3.96) and 1.43 (95% CI = 0.97 to 2.10) for 0 days of poor physical and mental health, respectively, and 2.61 (95% CI = 1.74 to 3.91) for good to excellent general health. Conclusions: Participating in LTPA was associated with improved health-related QoL. Interventions to promote LTPA and/or exercise-based rehabilitation may improve QoL among lung cancer survivors.

Association of Exercise Behavior with Overall Survival in Stage I-IIIA Lung Cancer.

Rationale: Exercise assessments may help predict outcomes for patients with diagnosed lung cancer. Objectives: We examined the relationship between prediagnosis exercise behavior and clinical outcomes among patients with stage I-IIIA lung cancer. Methods: In a retrospective cohort study of patients with stage I-IIIA lung cancer at Kaiser Permanente Colorado who had at least one Exercise Vital Sign assessment-a questionnaire tool to help promote exercise in chronic disease management-within the year before diagnosis, we defined exercise behavior as active (any min/wk of moderate-to-vigorous-intensity physical activity) or inactive (no moderate-to-vigorous physical activity). The outcomes were 1) overall survival (OS) and 2) acute healthcare use (AHCU). We used the Kaplan-Meier method, Cox proportional hazard model, and negative binomial regression model to analyze the effects of exercise on outcomes, adjusting for demographic, socioeconomic, clinical, and lung-cancer characteristics. Results: Among 552 patients with lung cancer, 230 (42%) were identified as physically active before their diagnosis of cancer. There was no significant difference in the stage distribution between active and inactive patients. The median survival times were 2.4 years for the active group and 1.8 years for inactive patients (P < 0.001). The mean rates (standard deviations) of AHCU were 1.09 (1.55) and 2.31 (5.61) per person-year for active and inactive groups, respectively (P < 0.01). Active exercise, compared with inactivity, was associated with better OS (hazard ratio, 0.52 [0.39-0.69]) and lower AHCU (rate ratio, 0.63 [0.49-0.80]) in unadjusted analyses; in adjusted analyses, active exercise was associated with better OS (hazard ratio, 0.62 [0.45-0.86]), but AHCU was not lower by a statistically significant amount (rate ratio, 0.82 [0.65-1.04]). Conclusions: Prediagnosis active exercise was associated with better OS after diagnosis of stage I-IIIA lung cancer. Exercise assessments may help predict outcomes, risk-stratify patients for curative-intent therapy, and identify those who would benefit from increased physical activity and exercise.

Effects of curative-intent lung cancer therapy on functional exercise capacity and patient-reported outcomes.

PURPOSE: Lung cancer treatment can lead to negative health consequences. We analyzed the effects of curative-intent lung cancer treatment on functional exercise capacity (EC) and patient-reported outcomes (PROs). METHODS: We performed a prospective, observational cohort study of consecutive patients with stage I-IIIA lung cancer undergoing curative-intent therapy and assessed functional EC (primary outcome, six-minute walk distance (6MWD)), cancer-specific quality of life (QoL) (secondary outcome, European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30) summary score), and exploratory outcomes including dyspnea (University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)) and fatigue Brief Fatigue Inventory (BFI)) symptoms before and at 1 to 3 months post-treatment. We analyzed the time effect of treatment on outcomes using multivariable generalized estimating equations. RESULTS: In 35 enrolled participants, treatment was associated with a clinically meaningful and borderline-significant decline in functional EC ((mean change, 95% CI) 6MWD = - 25.4 m (- 55.3, + 4.47), p = 0.10), clinically meaningful and statistically significant higher dyspnea (UCSD SOBQ = + 13.1 (+ 5.7, + 20.6), p = 0.001) and fatigue (BFI = + 10.0 (+ 2.9, + 17.0), p = 0.006), but no clinically meaningful or statistically significant change in cancer-specific QoL (EORTC-QLQ-C30 summary score = - 3.4 (- 9.8, + 3.0), p = 0.30). CONCLUSIONS: Among the first prospective analysis of the effect of curative-intent lung cancer treatment on functional EC and PROs, we observed worsening dyspnea and fatigue, and possibly a decline in functional EC but not cancer-specific QoL at 1 to 3 months post-treatment. Interventions to reduce treatment-related morbidities and improve lung cancer survivorship may need to focus on reducing dyspnea, fatigue, and/or improving functional EC.

Characterization of Dyspnea in Veteran Lung Cancer Survivors Following Curative-Intent Therapy.

PURPOSE: Dyspnea is highly prevalent in lung cancer survivors following curative-intent therapy. We aimed to identify clinical predictors or determinants of dyspnea and characterize its relationship with functional exercise capacity (EC). METHODS: In an analysis of data from a cross-sectional study of lung cancer survivors at the VA San Diego Healthcare System who completed curative-intent therapy for stage I-IIIA disease ≥1 mo previously, we tested a thorough list of comorbidities, lung function, and lung cancer characteristics. We assessed dyspnea using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (LC13) and functional EC using the 6-minute walk. We replicated results with the University of California San Diego Shortness of Breath Questionnaire. RESULTS: In 75 participants at a median of 12 mo since treatment completion, the mean ± SD LC13-Dyspnea score was 35.3 ± 26.2; 60% had abnormally high dyspnea. In multivariable linear regression analyses, significant clinical predictors or determinants of dyspnea were (ß [95% CI]) psychiatric illness (-20.8 [-32.4 to -9.09]), heart failure with reduced ejection fraction (-15.5 [-28.0 to -2.97]), and forced expiratory volume in the first second of expiration (-0.28 [-0.49 to -0.06]). Dyspnea was an independent predictor of functional EC (-1.54 [-2.43 to -0.64]). These results were similar with the University of California San Diego Shortness of Breath Questionnaire. CONCLUSION: We identified clinical predictors or determinants of dyspnea that have pathophysiological bases. Dyspnea was independently associated with functional EC. These results have implications in efforts to reduce dyspnea and improve exercise behavior and functional EC in lung cancer survivors following curative-intent therapy.

A Model-Based Cost-Effectiveness Analysis of an Exercise Program for Lung Cancer Survivors After Curative-Intent Treatment.

OBJECTIVE: The cost-effectiveness of exercise interventions in lung cancer survivors is unknown. We performed a model-based cost-effectiveness analysis of an exercise intervention in lung cancer survivors. DESIGN: We used Markov modeling to simulate the impact of the Lifestyle Interventions and Independence for Elders exercise intervention compared with usual care for stage I-IIIA lung cancer survivors after curative-intent treatment. We calculated and considered incremental cost-effectiveness ratios of less than US $100,000/quality-adjusted life-year as cost-effective and assessed model uncertainty using sensitivity analyses. RESULTS: The base-case model showed that the Lifestyle Interventions and Independence for Elders exercise program would increase overall cost by US $4740 and effectiveness by 0.06 quality-adjusted life-years compared with usual care and have an incremental cost-effectiveness ratio of US $79,504/quality-adjusted life-year. The model was most sensitive to the cost of the exercise program, probability of increasing exercise, and utility benefit related to exercise. At a willingness-to-pay threshold of US $100,000/quality-adjusted life-year, Lifestyle Interventions and Independence for Elders had a 71% probability of being cost-effective compared with 27% for usual care. When we included opportunity costs, Lifestyle Interventions and Independence for Elders had an incremental cost-effectiveness ratio of US $179,774/quality-adjusted life-year, exceeding the cost-effectiveness threshold. CONCLUSIONS: A simulation of the Lifestyle Interventions and Independence for Elders exercise intervention in lung cancer survivors demonstrates cost-effectiveness from an organization but not societal perspective. A similar exercise program for lung cancer survivors may be cost-effective.

Insights into acetate-mediated copper homeostasis and antioxidant defense in lentil under excessive copper stress.

Gradual contamination of agricultural land with copper (Cu), due to the indiscriminate uses of fungicides and pesticides, and the discharge of industrial waste to the environment, poses a high threat for soil degradation and consequently food crop production. In this study, we combined morphological, physiological and biochemical assays to investigate the mechanisms underlying acetate-mediated Cu toxicity tolerance in lentil. Results demonstrated that high dose of Cu (3.0 mM CuSO4. 5H2O) reduced seedling growth and chlorophyll content, while augmenting Cu contents in both roots and shoots, and increasing oxidative damage in lentil plants through disruption of the antioxidant defense. Principle component analysis clearly indicated that Cu accumulation and increased oxidative damage were the key factors for Cu toxicity in lentil seedlings. However, acetate pretreatment reduced Cu accumulation in roots and shoots, increased proline content and improved the responses of antioxidant defense (e.g. increased catalase and glutathione-S-transferase activities, and improved action of glutathione-ascorbate metabolic pathway). As a result, excess Cu-induced oxidative damage was reduced, and seedling growth was improved under Cu stress conditions, indicating the role of acetate in alleviating Cu toxicity in lentil seedlings. Taken together, exogenous acetate application reduced Cu accumulation in lentil roots and shoots and mitigated oxidative damage by activating the antioxidant defense, which were the major determinants for alleviating Cu toxicity in lentil seedlings. Our findings provide mechanistic insights into the protective roles of acetate in mitigating Cu toxicity in lentil, and suggest that application of acetate could be a novel and economical strategy for the management of heavy metal toxicity and accumulation in crops.

Heart rate variability and heart rate recovery in lung cancer survivors eligible for long-term cure.

Lung cancer survivors are at risk for physical fitness and autonomic function impairments. In a cross-sectional study of consecutive lung cancer survivors post-curative intent therapy, we assessed and identified predictors of resting heart rate variability (HRV) and heart rate recovery (HRR), defined as standard deviation of normal-to-normal-R-to-R intervals (SDNN) and root-mean-square-of-successive-differences (rMSSD) from routine outpatient single 10-s electrocardiographs (ECGs) and difference in heart rate (HR) at 1-minute following and the end of the six-minute-walk-test (6MWT), respectively. In 69 participants, the mean (SD) HRR was -10.6 (6.7) beats. Significant independent predictors of HRR were age and HR change associated with the 6MWT. In a subset of 41 participants with available ECGs, the mean (SD) SDNN and rMSSD were 19.1 (15.6) and rMSSD 18.2 (14.6) ms, respectively. Significant independent predictors of HRV were supine HR, HRR, and total lung capacity. HRV/HRR may be useful physiological measures in studies aimed at improving physical fitness and/or autonomic function in lung cancer survivors.

Time to treatment and survival in veterans with lung cancer eligible for curative intent therapy.

BACKGROUND: The Institute of Medicine emphasizes care timeliness as an important quality metric. We assessed treatment timeliness in stage I-IIIA lung cancer patients deemed eligible for curative intent therapy and analyzed the relationship between time to treatment (TTT) and timely treatment (TT) with survival. METHODS: We retrospectively reviewed consecutive cases of stage I-IIIA lung cancer deemed eligible for curative intent therapy at the VA San Diego Healthcare System between 10/2010-4/2017. We defined TTT as days from chest tumor board to treatment initiation and TT using guideline recommendations. We used multivariable (MVA) Cox proportional hazards regressions for survival analyses. RESULTS: In 177 veterans, the median TTT was 35 days (29 days for chemoradiation, 36 for surgical resection, 42 for definitive radiation). TT occurred in 33% or 77% of patients when the most or least timely guideline recommendation was used, respectively. Patient characteristics associated with longer TTT included other cancer history, high simplified comorbidity score, stage I disease, and definitive radiation treatment. In MVA, TTT and TT [HR 0.53 (95% CI 0.27, 1.01) for least timely definition] were not associated with OS in stage I-IIIA patients, or disease-free survival in subgroup analyses of 122 stage I patients [HR 1.49 (0.62, 3.59) for least timely definition]. CONCLUSION: Treatment was timely in 33-77% of veterans with lung cancer deemed eligible for curative intent therapy. TTT and TT were not associated with survival. The time interval between diagnosis and treatment may offer an opportunity to deliver or improve other cancer care.

Function of the evolutionarily conserved plant methionine-S-sulfoxide reductase without the catalytic residue.

In plants, two types of methionine sulfoxide reductase (MSR) exist, namely methionine-S-sulfoxide reductase (MSRA) and methionine-R-sulfoxide reductase (MSRB). These enzymes catalyze the reduction of methionine sulfoxides (MetO) back to methionine (Met) by a catalytic cysteine (Cys) and one or two resolving Cys residues. Interestingly, a group of MSRA encoded by plant genomes does not have a catalytic residue. We asked that if this group of MSRA did not have any function (as fitness), why it was not lost during the evolutionary process. To challenge this question, we analyzed the gene family encoding MSRA in soybean (GmMSRAs). We found seven genes encoding GmMSRAs, which included three segmental duplicated pairs. Among them, a pair of duplicated genes, namely GmMSRA1 and GmMSRA6, was without a catalytic Cys residue. Pseudogenes were ruled out as their transcripts were detected in various tissues and their Ka/Ks ratio indicated a negative selection pressure. In vivo analysis in Δ3MSR yeast strain indicated that the GmMSRA6 did not have activity toward MetO, contrasting to GmMSRA3 which had catalytic Cys and had activity. When exposed to H2O2-induced oxidative stress, GmMSRA6 did not confer any protection to the Δ3MSR yeast strain. Overexpression of GmMSRA6 in Arabidopsis thaliana did not alter the plant's phenotype under physiological conditions. However, the transgenic plants exhibited slightly higher sensitivity toward salinity-induced stress. Taken together, this data suggested that the plant MSRAs without the catalytic Cys are not enzymatically active and their existence may be explained by a role in regulating plant MSR activity via dominant-negative substrate competition mechanism.