Synthesis and base-pairing properties of pyrazine nucleic acids.

The diversity of backbone modifications in the study of primitive informational polymers is partly limited by the plausible formation of their prebiotic starting components. In this paper, we synthesize pyrazine nucleic acid, an acyclic polymer, with the nucleoside derivable from a prebiotic one-pot synthesis containing alanine amide and D-ribose. Pyrazine nucleic acid (PzNA) which has a backbone structurally similar to glycerol nucleic acid (GNA), contain pyrazine derived nucleosides as informational elements that may exhibit base pairing properties similar to the pyrimidines present in RNA.[1] We found that insertion of pyrazinone nucleotides into DNA oligonucleotide sequences is not well-tolerated, and that homogenous sequences of PzNA are unable to form duplexes with RNA or DNA. Reasons for our results may be attributed to the pyrazine-2-one moiety, which is purposed to be a thymine analog, but has a lower pKa (pKa ∼ 8.5) than thymine and uracil. Additionally, we discovered an "apparent" regioselective protection of pyrazine-2-one derivatives in the presence of a secondary hydroxyl group that proved crucial in the preparation of the pyrazine-2-one phosphoramidite. The regioselectivity observed is proposed to be of general interest in the context of heterocyclic chemistry. In the larger context of origins of life studies, it points to the importance of keto-enol preferences of the canonical nucleobases versus pyrazine heterocycles in functioning as recognition elements.

Home-based Physical Activity Coaching, Physical Activity, and Health Care Utilization in Chronic Obstructive Pulmonary Disease. Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial Secondary Outcomes.

RATIONALE: Physical inactivity among patients with chronic obstructive pulmonary disease is associated with exacerbations requiring high-cost health care utilization including urgent, emergent, and hospital care. OBJECTIVES: To examine the effectiveness of a behavioral lifestyle physical activity intervention combined with chronic obstructive pulmonary disease self-management education to prevent high-cost health care utilization. METHODS: This was an analysis of secondary outcomes of the Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial, a two-arm randomized trial of stable adult outpatients with chronic obstructive pulmonary disease recruited from primary care and pulmonary clinics. Following a 6-week self-management education run-in period, participants were randomized to usual care or to a telephone-delivered home-based health coaching intervention over 20 weeks. Secondary outcomes of physical activity and health care utilization were determined by self-report 6, 12, and 18 months after randomization. Associations between treatment allocation arm and these secondary outcomes were examined using log-binomial and Poisson regression models. RESULTS: A total of 325 outpatients with stable chronic obstructive pulmonary disease were enrolled in the trial. Their average age was 70.3 years (standard deviation, 9.5), and 50.5% were female; 156 were randomized to usual care and 149 to the intervention. A greater proportion of participants reported being persistently active over the 18-month follow-up period in the intervention group (73.6%) compared with the usual care group (57.8%) (mean difference, 15.8%; 95% confidence interval, 4.0-27.7%). This association varied by severity of forced expiratory volume in 1 second impairment (P for interaction = 0.09). Those in the intervention group with moderate impairment (forced expiratory volume in 1 second, 50-70% predicted), more frequently reported being persistently active compared with the usual care (86.0 vs. 65.1%; mean difference, 20.9%; 95% confidence interval, 5.7-36.1%). Patients with severe and very severe forced expiratory volume in 1 second impairment (forced expiratory volume in 1 second < 50% predicted) in the intervention group also reported being persistently active more frequently compared with usual care (63.3 vs. 50.8%; mean difference, 12.6%; 95% confidence interval, -4.7 to 29.8). The intervention was associated with a lower rate of lung-related utilization (adjusted rate ratio, 0.38; 95% confidence interval, 0.23-0.63) only among participants with severe spirometric impairment. CONCLUSIONS: Our results demonstrate that a feasible and generalizable home-based coaching intervention may decrease sedentary behavior and increase physical activity levels. In those with severe chronic obstructive pulmonary disease, this intervention may reduce lung disease-related health care utilization. Clinical trial registered with www.clinicaltrials.gov (NCT01108991).

A Lifestyle Physical Activity Intervention for Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

RATIONALE: Physical inactivity is associated with poor outcomes among patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine effectiveness of a behavioral intervention intended to increase daily physical activity with the goal of improving health-related quality of life and functional performance. METHODS: We conducted a randomized trial among patients with COPD cared for in primary care and pulmonary clinics. The patients were at least 45 years of age and eligible for pulmonary rehabilitation. All patients received self-management education during a 6-week run-in period. Subsequently, patients were randomized to usual care or the intervention delivered over 20 weeks. MEASUREMENTS AND MAIN RESULTS: Co-primary outcomes were change from baseline in Chronic Respiratory Questionnaire dyspnea domain score and 6-minute-walk distance measured at 6, 12, and 18 months after randomization. A total of 325 patients were enrolled, with 156 randomized to receive usual care and 149 to receive the intervention. At 18 months, there was no overall statistical or clinically significant change in the dyspnea domain in either group. However, for 6-minute-walk distance, there were statistically significant declines in both groups. In contrast, 6-minute-walk distance remained stable (5.3 m; P = 0.54) among patients in the intervention group with moderate spirometric impairment, but it was associated with clinically and statistically significant declines (-28.7 m; P = 0.0001) among usual care patients with moderate spirometric impairment. Overall, there was no increase in adverse events associated with the intervention, which was associated with a lower prevalence of hospitalization for COPD exacerbations (28.3%) compared with usual care (49.5%). CONCLUSIONS: During this 18-month trial among outpatients with COPD, a health coach-based behavioral intervention did not improve scores in the dyspnea domain of the Chronic Respiratory Questionnaire or 6-minute-walk test distance. However, subgroup analyses suggested that there may be differential effects for specific outcomes that vary with severity of COPD. Specifically, benefits of this low-intensity intervention may be limited to 6-minute walk distance among patients with moderate spirometric impairment. Clinical trial registered with www.clinicaltrials.gov (NCT1108991).

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment and baseline patient characteristics.

OBJECTIVE: To describe the recruitment methods, study participation rate, and baseline characteristics of a representative sample of outpatients with COPD eligible for pulmonary rehabilitation participating in a trial of a lifestyle behavioral intervention to increase physical activity. SETTING AND DESIGN: A patient registry was developed for recruitment using an administrative database from primary care and specialty clinics of an academic medical center in northeast Texas for a parallel group randomized trial. RESULTS: The registry was comprised of 5582 patients and over the course of the 30 month recruitment period 325 patients were enrolled for an overall study participation rate of 35.1%. After a 6-week COPD self-management education period provided to all enrolled patients, 305 patients were randomized into either usual care (UC; n=156) or the physical activity self-management intervention (PASM; n=149). There were no clinically significant differences in demographics, clinical characteristics, or health status indicators between the randomized groups. CONCLUSION: The results of this recruitment process demonstrate the successful use of a patient registry for enrolling a representative sample of outpatients eligible for pulmonary rehabilitation with COPD from primary and specialty care. Moreover, this approach to patient recruitment provides a model for future studies utilizing administrative databases and electronic health records.

Domain-specific self-efficacy is associated with measures of functional capacity and quality of life among patients with moderate to severe chronic obstructive pulmonary disease.

RATIONALE: The relationship between self-efficacy and health behaviors is well established. However, little is known about the relationship between self-efficacy and health-related indicators among patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The purpose of this cross-sectional cohort study was to test the hypothesis that the total score and specific subdomain scores of the COPD Self-Efficacy Scale (CSES) are associated with functional capacity and quality of life in a group of patients with moderate to severe COPD. METHODS: Relationships were examined in a cross-sectional study of baseline data collected as part of a randomized trial. Self-efficacy was measured using the five domains of the CSES: negative affect, emotional arousal, physical exertion, weather/environment, and behavioral. Measures of quality of life and functional capacity included SF-12: physical and mental composite scores, Chronic Respiratory Questionnaire dyspnea domain, and the 6-minute-walk test. Statistical analyses included Spearman correlation and categorical analyses of self-efficacy ("confident" vs. "not confident") using general linear models adjusting for potential confounders. MEASUREMENTS AND MAIN RESULTS: There were 325 patients enrolled with a mean age (standard deviation) of 68.5 (9.48) years, 49.5% male, and 91.69% non-Hispanic white. The negative affect, emotional arousal, and physical exertion domains were moderately correlated (range, 0.3-0.7) with the SF-12 mental composite score and Chronic Respiratory Questionnaire dyspnea domain. In models exploring each CSES domain as "confident" versus "not confident" and adjusting for age, sex, race, pack-years, and airflow obstruction severity, there were multiple clinically and statistically significant associations between the negative affect, emotional arousal, and physical exertion domains with functional capacity and quality of life. CONCLUSIONS: The aggregated total CSES score was associated with better quality of life and functional capacity. Our analysis of subdomains revealed that the physical exertion, negative affect, and emotional arousal subdomains had the largest associations with functional capacity and quality of life indicators. These findings suggest that interventions to enhance self-efficacy may improve the functional capacity and quality of life of patients with moderate to severe COPD.

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): design and methods.

BACKGROUND: Treatment of COPD requires multiple pharmacological and non-pharmacological intervention strategies. One target is physical inactivity because it leads to disability and contributes to poor physical and mental health. Unfortunately, less than 1% of eligible patients have access to gold-standard pulmonary rehabilitation. METHODS: A single-site parallel group randomized trial was designed to determine if a self-management lifestyle physical activity intervention would improve physical functioning and dyspnea. During the first six weeks after enrollment patients receive COPD self-management education delivered by a health coach using a workbook and weekly telephone calls. Patients are then randomized to usual care or the physical activity intervention. The 20 week physical activity intervention is delivered by the health coach using a workbook supported by alternating one-on-one telephone counseling and computer assisted telephone calls. Theoretical foundations include social cognitive theory and the transtheoretical model. RESULTS: Primary outcomes include change in Chronic Respiratory Questionnaire (CRQ) dyspnea domain and 6-minute walk distance measured at 6-, 12-, and 18-months after randomization. Secondary outcomes include other CRQ domains (fatigue, emotion, and mastery), SF-12, and health care utilization. Other measures include process outcomes and clinical characteristics. CONCLUSIONS: This theory driven self-management lifestyle physical activity intervention is designed to reach patients unable to complete center-based pulmonary rehabilitation. Results will advance knowledge and methods for dissemination of a potentially cost-effective program for patients with COPD.