OpenChemIE: An Information Extraction Toolkit for Chemistry Literature.

Information extraction from chemistry literature is vital for constructing up-to-date reaction databases for data-driven chemistry. Complete extraction requires combining information across text, tables, and figures, whereas prior work has mainly investigated extracting reactions from single modalities. In this paper, we present OpenChemIE to address this complex challenge and enable the extraction of reaction data at the document level. OpenChemIE approaches the problem in two steps: extracting relevant information from individual modalities and then integrating the results to obtain a final list of reactions. For the first step, we employ specialized neural models that each address a specific task for chemistry information extraction, such as parsing molecules or reactions from text or figures. We then integrate the information from these modules using chemistry-informed algorithms, allowing for the extraction of fine-grained reaction data from reaction condition and substrate scope investigations. Our machine learning models attain state-of-the-art performance when evaluated individually, and we meticulously annotate a challenging dataset of reaction schemes with R-groups to evaluate our pipeline as a whole, achieving an F1 score of 69.5%. Additionally, the reaction extraction results of OpenChemIE attain an accuracy score of 64.3% when directly compared against the Reaxys chemical database. OpenChemIE is most suited for information extraction on organic chemistry literature, where molecules are generally depicted as planar graphs or written in text and can be consolidated into a SMILES format. We provide OpenChemIE freely to the public as an open-source package, as well as through a web interface.

Chronic respiratory symptoms following deployment-related occupational and environmental exposures among US veterans.

OBJECTIVES: Characterise inhalational exposures during deployment to Afghanistan and Southwest Asia and associations with postdeployment respiratory symptoms. METHODS: Participants (n=1960) in this cross-sectional study of US Veterans (Veterans Affairs Cooperative Study 'Service and Health Among Deployed Veterans') completed an interviewer-administered questionnaire regarding 32 deployment exposures, grouped a priori into six categories: burn pit smoke; other combustion sources; engine exhaust; mechanical and desert dusts; toxicants; and military job-related vapours gas, dusts or fumes (VGDF). Responses were scored ordinally (0, 1, 2) according to exposure frequency. Factor analysis supported item reduction and category consolidation yielding 28 exposure items in 5 categories. Generalised linear models with a logit link tested associations with symptoms (by respiratory health questionnaire) adjusting for other covariates. OR were scaled per 20-point score increment (normalised maximum=100). RESULTS: The cohort mean age was 40.7 years with a median deployment duration of 11.7 months. Heavy exposures to multiple inhalational exposures were commonly reported, including burn pit smoke (72.7%) and VGDF (72.0%). The prevalence of dyspnoea, chronic bronchitis and wheeze in the past 12 months was 7.3%, 8.2% and 15.6%, respectively. Burn pit smoke exposure was associated with dyspnoea (OR 1.22; 95% CI 1.06 to 1.47) and chronic bronchitis (OR 1.22; 95% CI 1.13 to 1.44). Exposure to VGDF was associated with dyspnoea (OR 1.29; 95% CI 1.14 to 1.58) and wheeze (OR 1.18; 95% CI 1.02 to 1.35). CONCLUSION: Exposures to burn pit smoke and military occupational VGDF during deployment were associated with an increased odds of chronic respiratory symptoms among US Veterans.

Inflammatory Markers and Fatigue in Individuals With Moderate to Severe Chronic Obstructive Pulmonary Disease.

BACKGROUND: Fatigue, a prevalent complex symptom among patients with chronic obstructive pulmonary disease (COPD), is considered an important clinical indicator of disease severity. However, the underlying mechanisms of COPD-related fatigue are not fully understood. OBJECTIVES: This analysis explored the relationships between peripheral inflammatory markers and COPD-related fatigue in people with moderate to severe COPD. METHODS: This is a secondary analysis of a longitudinal observational study of individuals with COPD examining the biological causes and functional consequences of depression. The data used in this study were collected at baseline. Systemic inflammation markers included C-reactive protein (CRP) and three pro-inflammatory cytokines consisting of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α. COPD-related fatigue was self-reported using the Chronic Respiratory Questionnaire. Covariates included age; gender; smoking status; disease severity; symptoms of depression, anxiety, and pain; and social support. Multivariable linear regression analyses were conducted. RESULTS: The sample included 300 adults living with COPD; 80% were male, and the average age was 67.6 years. Modest correlations were found between two systemic inflammatory markers (CRP and IL-8) and COPD-related fatigue. CRP was the only inflammatory marker significantly associated with fatigue symptoms after adjusting for covariates in multivariable analyses. Depression, pain, and education level were also significant predictors of COPD-related fatigue. DISCUSSION: The findings suggest that altered immune response based on CRP may contribute to COPD-related fatigue. Management of depression and pain may work as an effective treatment strategy for COPD-related fatigue. Further longitudinal studies with a broader range of inflammatory markers and multidimensional measures of fatigue symptoms are warranted.

Clinicians' use of Health Information Exchange technologies for medication reconciliation in the U.S. Department of Veterans Affairs: a qualitative analysis.

BACKGROUND: Medication reconciliation is essential for optimizing medication use. In part to promote effective medication reconciliation, the Department of Veterans Affairs (VA) invested substantial resources in health information exchange (HIE) technologies. The objectives of this qualitative study were to characterize VA clinicians' use of HIE tools for medication reconciliation in their clinical practice and to identify facilitators and barriers. METHODS: We recruited inpatient and outpatient prescribers (physicians, nurse practitioners, physician assistants) and pharmacists at four geographically distinct VA medical centers for observations and interviews. Participants were observed as they interacted with HIE or medication reconciliation tools during routine work. Participants were interviewed about clinical decision-making pertaining to medication reconciliation and use of HIE tools, and about barriers and facilitators to use of the tools. Qualitative data were analyzed via inductive and deductive approaches using a priori codes. RESULTS: A total of 63 clinicians participated. Over half (58%) were female, and the mean duration of VA clinical experience was 7 (range 0-32) years. Underlying motivators for clinicians seeking data external to their VA medical center were having new patients, current patients receiving care from an external institution, and clinicians' concerns about possible medication discrepancies among institutions. Facilitators for using HIE software were clinicians' familiarity with the HIE software, clinicians' belief that medication information would be available within HIE, and their confidence in the ability to find HIE medication-related data of interest quickly. Six overarching barriers to HIE software use for medication coordination included visual clutter and information overload within the HIE display; challenges with HIE interface navigation; lack of integration between HIE and other electronic health record interfaces, necessitating multiple logins and application switching; concerns with the dependability of HIE medication information; unfamiliarity with HIE tools; and a lack of HIE data from non-VA facilities. CONCLUSIONS: This study is believed to be the first to qualitatively characterize clinicians' HIE use with respect to medication reconciliation. Results inform recommendations to optimize HIE use for medication management activities. We expect that healthcare organizations and software vendors will be able to apply the findings to develop more effective and usable HIE information displays.

Trends Over Time in the Risk of Adverse Outcomes Among Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: We aimed to describe trends in adverse outcomes among patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between February and September 2020 within a national healthcare system. METHODS: We identified enrollees in the national United States Veterans Affairs healthcare system who tested positive for SARS-CoV-2 between 28 February 2020 and 30 September 2020 (n = 55 952), with follow-up extending to 19 November 2020. We determined trends over time in incidence of the following outcomes that occurred within 30 days of testing positive: hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death. RESULTS: Between February and July 2020, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), which subsequently plateaued between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, documented symptoms, and laboratory tests, including among subgroups of patients hospitalized, admitted to the ICU, or treated with mechanical ventilation. From February to September, there were decreases in the use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%), vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) and increases in the use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%), and remdesivir (1.7% to 45.4%) among hospitalized patients. CONCLUSIONS: The risk of adverse outcomes in SARS-CoV-2-positive patients decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics and may reflect changing treatment practices or viral pathogenicity.

Cirrhosis and Severe Acute Respiratory Syndrome Coronavirus 2 Infection in US Veterans: Risk of Infection, Hospitalization, Ventilation, and Mortality.

BACKGROUND AND AIMS: Whether patients with cirrhosis have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which infection and cirrhosis increase the risk of adverse patient outcomes remain unclear. APPROACH AND RESULTS: We identified 88,747 patients tested for SARS-CoV-2 between March 1, 2020, and May 14, 2020, in the Veterans Affairs (VA) national health care system, including 75,315 with no cirrhosis-SARS-CoV-2-negative (C0-S0), 9,826 with no cirrhosis-SARS-CoV-2-positive (C0-S1), 3,301 with cirrhosis-SARS-CoV-2-negative (C1-S0), and 305 with cirrhosis-SARS-CoV-2-positive (C1-S1). Patients were followed through June 22, 2020. Hospitalization, mechanical ventilation, and death were modeled in time-to-event analyses using Cox proportional hazards regression. Patients with cirrhosis were less likely to test positive than patients without cirrhosis (8.5% vs. 11.5%; adjusted odds ratio, 0.83; 95% CI, 0.69-0.99). Thirty-day mortality and ventilation rates increased progressively from C0-S0 (2.3% and 1.6%) to C1-S0 (5.2% and 3.6%) to C0-S1 (10.6% and 6.5%) and to C1-S1 (17.1% and 13.0%). Among patients with cirrhosis, those who tested positive for SARS-CoV-2 were 4.1 times more likely to undergo mechanical ventilation (adjusted hazard ratio [aHR], 4.12; 95% CI, 2.79-6.10) and 3.5 times more likely to die (aHR, 3.54; 95% CI, 2.55-4.90) than those who tested negative. Among patients with SARS-CoV-2 infection, those with cirrhosis were more likely to be hospitalized (aHR, 1.37; 95% CI, 1.12-1.66), undergo ventilation (aHR, 1.61; 95% CI, 1.05-2.46) or die (aHR, 1.65; 95% CI, 1.18-2.30) than patients without cirrhosis. Among patients with cirrhosis and SARS-CoV-2 infection, the most important predictors of mortality were advanced age, cirrhosis decompensation, and high Model for End-Stage Liver Disease score. CONCLUSIONS: SARS-CoV-2 infection was associated with a 3.5-fold increase in mortality in patients with cirrhosis. Cirrhosis was associated with a 1.7-fold increase in mortality in patients with SARS-CoV-2 infection.

Caregiver Experiences and Roles in Care Seeking During COPD Exacerbations: A Qualitative Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating illness characterized by exacerbations that require timely intervention. COPD patients often rely on informal caregivers-relatives or friends-for assistance with functioning and support. Caregivers perform roles that may be particularly important during acute exacerbations in monitoring symptoms and seeking medical intervention. However, little is known about caregivers' roles and experiences as they support their patients during exacerbations. PURPOSE: To explore the experiences, roles in care seeking, and needs of caregivers during COPD exacerbations. METHODS: Semi-structured interviews were conducted with 24 caregivers of Veterans with COPD who experienced a recent exacerbation. Interviews were recorded, transcribed, and analyzed using inductive content analysis. RESULTS: Five themes arose: (a) caregivers reported continuously monitoring changes in patients symptom severity to identify exacerbations; (b) caregivers described emotional reactions evoked by exacerbations and constant vigilance; (c) caregivers described disagreements with their patient in interpreting symptoms and determining the need for care seeking; (d) caregivers noted uncertainty regarding their roles and responsibilities in pursuing care and their approaches to promote care varied; and (e) expressed their need for additional information and support. Caregivers of patients with COPD often influence whether and when patients seek care during exacerbations. Discrepancies in symptom evaluations between patients and caregivers paired with the lack of information and support available to caregivers are related to delays in care seeking. Clinical practice should foster self-management support to patient-caregiver dyads to increase caregiver confidence and patient openness to their input during exacerbations.

Potential Explanatory Factors for the Concurrent Experience of Dyspnea and Pain in Patients with COPD.

Previous research has identified unexpectedly strong associations between dyspnea and pain, but the reasons remain unclear. Ascertaining the underlying biological and psychological mechanisms might enhance the understanding of the experience of both conditions, and suggest novel treatments. We sought to elucidate whether demographic factors, disease severity, psychological symptoms and biomarkers might account for the association between pain and dyspnea in individuals with COPD. We analyzed data from 301 patients with COPD who were followed in a prospective longitudinal observational study over 2 years. Measures included self-reported dyspnea and pain, pulmonary function tests, serum levels of inflammatory cytokines, measures of physical deconditioning, and scales for depression and anxiety. Analyses involved cross-sectional and longitudinal linear regression models. Pain and dyspnea were strongly correlated cross-sectionally (r = 0.77, 95% CI 0.72-0.82) and simultaneously across time (r = 0.42, 95% CI 0.28-0.56). Accounting for any of the other health factors only slightly mitigated the associations. Symptoms of pain and dyspnea thus may be fundamentally linked in COPD, rather than being mediated by common biological, psychological, or functional factors. From the patient's perspective, pain and dyspnea may be part of the same essential experience. It is possible that treatments for one condition would improve the other.

Risk Factors for Testing Positive for Severe Acute Respiratory Syndrome Coronavirus 2 in a National United States Healthcare System.

BACKGROUND: Identifying risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could help health systems improve testing and screening strategies. The aim of this study was to identify demographic factors, comorbid conditions, and symptoms independently associated with testing positive for SARS-CoV-2. METHODS: This was an observational cross-sectional study at the Veterans Health Administration, including persons tested for SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR) between 28 February and 14 May 2020. Associations between demographic characteristics, diagnosed comorbid conditions, and documented symptoms with testing positive for SARS-CoV-2 were measured. RESULTS: Of 88 747 persons tested, 10 131 (11.4%) were SARS-CoV-2 PCR positive. Positivity was associated with older age (≥80 vs <50 years: adjusted odds ratio [aOR], 2.16 [95% confidence interval {CI}, 1.97-2.37]), male sex (aOR, 1.45 [95% CI, 1.34-1.57]), regional SARS-CoV-2 burden (≥2000 vs <400 cases/million: aOR, 5.43 [95% CI, 4.97-5.93]), urban residence (aOR, 1.78 [95% CI, 1.70-1.87]), black (aOR, 2.15 [95% CI, 2.05-2.26]) or American Indian/Alaska Native Hawaiian/Pacific Islander (aOR, 1.26 [95% CI, 1.05-1.52]) vs white race, and Hispanic ethnicity (aOR, 1.52 [95% CI, 1.40-1.65]). Obesity and diabetes were the only 2 medical conditions associated with testing positive. Documented fevers, chills, cough, and diarrhea were also associated with testing positive. The population attributable fraction of positive tests was highest for geographic location (35.3%), followed by demographic variables (27.1%), symptoms (12.0%), obesity (10.5%), and diabetes (0.4%). CONCLUSIONS: The majority of positive SARS-CoV-2 tests were attributed to geographic location, demographic characteristics, and obesity, with a minor contribution of chronic comorbid conditions.

Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.

Sociodemographic Characteristics and Physical Activity in Patients with COPD: A 3-Month Cohort Study.

Decreased physical activity (PA) is associated with morbidity and mortality in COPD patients. In this secondary analysis of data from a 12-week longitudinal study, we describe factors associated with PA in COPD. Participants completed the Physical Activity Checklist (PAC) daily for a 7- to 8-day period. PA was measured monthly using the Physical Activity Scale for the Elderly (PASE). At three different time points, daily step count was measured for one week with an Omron HJ-720ITC pedometer. The 35 participants were primarily male (94%) and White (91%), with an average age of 66.5 years and FEV1 44.9% predicted. Common activities reported on the PAC were walking (93%), preparing a meal (89%), and traveling by vehicle (96%). PA measured by both PASE score (p = 0.01) and average daily step count (p = 0.04) decreased during follow-up. In repeated measures multivariable modeling, participants living with others had a higher daily step count (ß = 942 steps, p = 0.01) and better PASE scores (ß = 46.4, p < 0.001). Older age was associated with decreased step count (ß = -77 steps, p < 0.001) whereas White race was associated with lower PASE scores (ß = -55.4, p < 0.001) compared to non-White race. Other demographic factors, quality of life, and medications were not associated with PA. A better understanding of the role of social networks and social support may help develop interventions to improve PA in COPD.

Comparing the Barriers and Facilitators of Heart Failure Management as Perceived by Patients, Caregivers, and Clinical Providers.

BACKGROUND: Heart failure (HF) management requires the participation of patients, their significant others, and clinical providers. Each group may face barriers to HF management that may be unique or may overlap. OBJECTIVE: The aim of this study was to compare the barriers and facilitators of HF management as perceived by patients, significant others, and clinical providers. METHODS: Participants were recruited from a Veterans Health Administration facility. Eligible patients had a diagnosis of HF (ICD9 code 428.XX), 1 or more HF-related visit in the previous year, and a significant other who was their primary caregiver. Significant others were adults with no history of cognitive impairments caring for patients with HF. Providers were eligible if they cared for patients with HF. All participants completed semistructured interviews designed to elicit barriers to managing HF and strategies that they used to overcome these barriers. Interviews were transcribed and analyzed using latent thematic analysis, and recruitment continued until thematic saturation was attained. RESULTS: A total of 17 couples and 12 providers were recruited. All 3 groups identified poor communication as a key barrier to HF management, including communication between patients and their significant other, between couples and providers, and providers with each other. Significant others noted that the lack of direct communication with clinical providers hindered their efforts to care for the patient. All 3 groups emphasized the importance of family members in optimizing adherence to HF self-management recommendations. CONCLUSIONS: Providers, patients, and significant others all play important and distinct roles in the management of HF. Tools to enhance communication and collaboration for all 3 and supporting the needs of significant others are missing components of current HF care.

Using Video Telehealth to Facilitate Inhaler Training in Rural Patients with Obstructive Lung Disease.

BACKGROUND: Proper inhaler technique is important for effective drug delivery and symptom control in chronic obstructive pulmonary disease (COPD) and asthma, yet not all patients receive inhaler instructions. INTRODUCTION: Using a retrospective chart review of participants in a video telehealth inhaler training program, the study compared inhaler technique within and between monthly telehealth visits and reports associated with patient satisfaction. MATERIALS AND METHODS: Seventy-four (N = 74) rural patients prescribed ≥1 inhaler participated in three to four pharmacist telehealth inhaler training sessions using teach-to-goal (TTG) methodology. Within and between visit inhaler technique scores are compared, with descriptive statistics of pre- and postprogram survey results including program satisfaction and computer technical issues. Healthcare utilization is compared between pre- and post-training periods. RESULTS: Sixty-nine (93%) patients completed all three to four video telehealth inhaler training sessions. During the initial visit, patients demonstrated improvement in inhaler technique for metered dose inhalers (albuterol, budesonide/formoterol), dry powder inhalers (formoterol, mometasone, tiotropium), and soft mist inhalers (ipratropium/albuterol) (p < 0.01 for all). Improved inhaler technique was sustained at 2 months (p < 0.01). Ninety-four percent of participants were satisfied with the program. Although technical issues were common, occurring among 63% of attempted visits, most of these visits (87%) could be completed. There was no significant difference in emergency department visits and hospitalizations pre- and post-training. DISCUSSION: This study demonstrated high patient acceptance of video telehealth training and objective improvement in inhaler technique. CONCLUSIONS: Video telehealth inhaler training using the TTG methodology is a promising program that improved inhaler technique and access to inhaler teaching for rural patients with COPD or asthma.

Association of ambient pollution with inhaler use among patients with COPD: a panel study.

BACKGROUND: Studies have linked ambient air pollution to chronic obstructive pulmonary disease (COPD) healthcare encounters. However, the association between air quality and rescue medication use is unknown. OBJECTIVES: We assessed the role of air pollution exposure for increased short-acting beta-2-agonist (SABA) use in patients with COPD through use of remote monitoring technology. METHODS: Participants received a portable electronic inhaler sensor to record the date, time and location for SABA use over a 3-month period. Ambient air pollution data and meteorological data were collected from a centrally located federal monitoring station. Mixed-effects Poisson regression was used to examine the association of daily inhaler use with pollutant levels. Four criteria pollutants (PM2.5, PM10, O3 and NO2), two particulate matter species (elemental carbon (EC) and organic carbon), estimated coarse fraction of PM10 (PM10-2.5) and four multipollutant air quality measures were each examined separately, adjusting for covariates that passed a false discovery rate (FDR) screening. RESULTS: We enrolled 35 patients with COPD (94.3% male and mean age: 66.5±8.5) with a mean forced expiratory volume in 1 s (FEV1) % predicted of 44.9+17.2. Participants had a median of 92 observation days (range 52-109). Participants' average SABA inhaler use ranged from 0.4 to 13.1 puffs/day (median 2.8). Controlling for supplemental oxygen use, long-acting anticholinergic use, modified Medical Research Council Dyspnoea Scale and influenza season, an IQR increase in PM10 concentration (8.0 µg/m3) was associated with a 6.6% increase in daily puffs (95% CI 3.5% to 9.9%; FDR <0.001). NO2 and EC concentration were also significantly associated with inhaler use (3.9% and 2.9% per IQR increase, respectively). CONCLUSIONS: Exposure to increased ambient air pollution were associated with a significant increase in SABA use for patients with COPD residing in a low-pollution area.

Applying the pragmatic-explanatory continuum indicator summary to the implementation of a physical activity coaching trial in chronic obstructive pulmonary disease.

BACKGROUND: Observational studies show that physical inactivity is associated with worse outcomes in chronic obstructive pulmonary disease (COPD). Despite practice guidelines recommending regular physical activity (PA), there are no large-scale experimental studies to confirm that patients at high risk for COPD exacerbations can increase their PA and consequently, have improved outcomes. PURPOSE: The purpose of this case study is to describe the use of a widely accepted pragmatic trials framework for the design and implementation of a pragmatic clinical trial (PCT) of PA coaching for COPD in a real-world setting. METHOD: The aim of the trial was to determine the effectiveness of a 12-month PA coaching intervention (Walk On!) compared to standard care for 2,707 patients at high risk for COPD exacerbations from a large integrated health care system. The descriptions of our implementation experiences are anchored within the pragmatic-explanatory continuum indicator summary (PRECIS-2) framework. DISCUSSION: Facilitators of PCT implementation include early and ongoing engagement and support of multiple stakeholders including patients, health system leaders, administrators, physician champions, and frontline clinicians, an organizational/setting that prioritizes positive lifestyle behaviors, and a flexible intervention that allows for individualization. Pragmatic challenges include reliance on electronic data that are not complete or available in real-time for patient identification, timing of outreach may not synchronize with patients' readiness for change, and high turnover of clinical staff drawn from the existing workforce. DISCUSSION: PRECIS-2 is a useful guide for organizing decisions about study designs and implementation approaches to help diverse stakeholders recognize the compromises between internal and external validity with those decisions.

Association Between Mental Health Staffing Level and Primary Care-Mental Health Integration Level on Provision of Depression Care in Veteran's Affairs Medical Facilities.

We examined the association of mental health staffing and the utilization of primary care/mental health integration (PCMHI) with facility-level variations in adequacy of psychotherapy and antidepressants received by Veterans with new, recurrent, and chronic depression. Greater likelihood of adequate psychotherapy was associated with increased (1) PCMHI utilization by recurrent depression patients (AOR 1.02; 95% CI 1.00, 1.03); and (2) staffing for recurrent (AOR 1.03; 95% CI 1.01, 1.06) and chronic (AOR 1.02; 95% CI 1.00, 1.03) depression patients (p < 0.05). No effects were found for antidepressants. Mental health staffing and PCMHI utilization explained only a small amount of the variance in the adequacy of depression care.

Definition of a COPD self-management intervention: International Expert Group consensus.

There is an urgent need for consensus on what defines a chronic obstructive pulmonary disease (COPD) self-management intervention. We aimed to obtain consensus regarding the conceptual definition of a COPD self-management intervention by engaging an international panel of COPD self-management experts using Delphi technique features and an additional group meeting.In each consensus round the experts were asked to provide feedback on the proposed definition and to score their level of agreement (1=totally disagree; 5=totally agree). The information provided was used to modify the definition for the next consensus round. Thematic analysis was used for free text responses and descriptive statistics were used for agreement scores.In total, 28 experts participated. The consensus round response rate varied randomly over the five rounds (ranging from 48% (n=13) to 85% (n=23)), and mean definition agreement scores increased from 3.8 (round 1) to 4.8 (round 5) with an increasing percentage of experts allocating the highest score of 5 (round 1: 14% (n=3); round 5: 83% (n=19)).In this study we reached consensus regarding a conceptual definition of what should be a COPD self-management intervention, clarifying the requisites for such an intervention. Operationalisation of this conceptual definition in the near future will be an essential next step.

Symptom profiles and inflammatory markers in moderate to severe COPD.

BACKGROUND: Physical and psychological symptoms are the hallmark of patients' subjective perception of their illness. The purpose of this analysis was to determine if patients with COPD have distinctive symptom profiles and to examine the association of symptom profiles with systemic biomarkers of inflammation. METHODS: We conducted latent class analyses of three physical (dyspnea, fatigue, and pain) and two psychological symptoms (depression and anxiety) in 302 patients with moderate to severe COPD using baseline data from a longitudinal observational study of depression in COPD. Systemic inflammatory markers included IL1, IL8, IL10, IL12, IL13, INF, GM-CSF, TNF-α (levels >75thcentile was considered high); and CRP (levels >3 mg/L was considered high). Multinominal logistic regression models were used to examine the association between symptom classes and inflammation while adjusting for key socio-demographic and disease characteristics. RESULTS: We found that a 4-class model best fit the data: 1) low physical and psychological symptoms (26%, Low-Phys/Low-Psych), 2) low physical but moderate psychological symptoms (18%, Low-Phys/Mod Psych), 3) high physical but moderate psychological symptoms (25%, High-Phys/Mod Psych), and 4) high physical and psychological symptoms (30%, High-Phys/High Psych). Unadjusted analyses showed associations between symptom class with high levels of IL7, IL-8 (p ≤ .10) and CRP (p < .01). In the adjusted model, those with a high CRP level were less likely to be in the High-Phys/Mod-Psych class compared to the Low-Phys/Low-Psych (OR: 0.41, 95%CI 0.19, 0.90) and Low-Phys/Mod-Psych classes (OR: 0.35, 95%CI 0.16, 0.78); elevated CRP was associated with in increased odds of being in the High-Phys/High-Psych compared to the High-Phys/Mod-Psych class (OR: 2.22, 95%CI 1.08, 4.58). Younger age, having at least a college education, oxygen use and depression history were more prominent predictors of membership in the higher symptom classes. CONCLUSIONS: Patients with COPD can be classified into four distinct symptom classes based on five commonly co-occurring physical and psychological symptoms. Systemic biomarkers of inflammation were not associated with symptom class. Additional work to test the reliability of these symptom classes, their biological drivers and their validity for prognostication and tailoring therapy in larger and more diverse samples is needed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01074515 .

Disability and recovery of independent function in obstructive lung disease: the cardiovascular health study.

BACKGROUND: Chronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time. OBJECTIVE: To identify factors associated with transition between states of disability and independent function in obstructive lung disease. METHODS: We analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 instrumental activity of daily living (IADL) or ≥1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression. RESULTS: The prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked ≥28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and <7 blocks: RR 0.73 and 95% CI 0.61-0.86). Increased strength (RR 1.16 and 95% CI 1.05-1.29) was associated with resolving IADL impairment. CONCLUSIONS: Disability is common in older people, especially in those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research is needed on interventions to improve these factors among patients with obstructive lung disease and disability.

Bidirectional relationship between cognitive function and pneumonia.

RATIONALE: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems. OBJECTIVES: To determine bidirectional relationships between cognition and pneumonia. METHODS: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate. MEASUREMENTS AND MAIN RESULTS: Of the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (ß = -0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62-3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections. CONCLUSIONS: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence.