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.

Biomarkers of Inflammation and Longitudinal Evaluation of Lung Function, Physical Activity, and Grip Strength: A Secondary Analysis in the CASCADE Study.

Rationale: Physical activity, lung function, and grip strength are associated with exacerbations, hospitalizations, and mortality in people with chronic obstructive pulmonary disease (COPD). We tested whether baseline inflammatory biomarkers were associated with longitudinal outcomes of these physiologic measurements. Methods: The COPD Activity: Serotonin Transporter, Cytokines, and Depression (CASCADE) study was a prospective observational study of individuals with COPD. Fourteen inflammatory biomarkers were measured at baseline. Participants were followed for 2 years. We analyzed associations between baseline biomarkers and FEV1, physical activity, and grip strength. We used a hierarchical hypothesis testing procedure to reduce type I error. We used Pearson correlations to test associations between baseline biomarkers and longitudinal changes in the outcomes of interest. We used Fisher's linear discriminant analysis to test if linear combinations of baseline biomarkers predict rapid FEV1 decline. Finally, we used linear mixed modeling to test associations between baseline biomarkers and outcomes of interest at baseline, year 1, and year 2; models were adjusted for age, smoking status, baseline biomarkers, and FEV1. Results: 302 participants (age 67.5 ± 8.5 years, 19.5% female, 28.5% currently smoking) were included. Baseline biomarkers were not associated with longitudinal changes in grip strength, physical activity, or rapid FEV1 decline. Higher IL-6 and CRP were associated with lower physical activity at baseline and these relationships persisted at year 1 and year 2. Conclusion: Baseline inflammatory biomarkers did not predict changes in lung function or physical activity, but higher inflammatory biomarkers were associated with persistently low levels of physical activity.

Deployment-related Cigarette Smoking Behaviors and Pulmonary Function Among U.S. Veterans.

INTRODUCTION: The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood. MATERIALS AND METHODS: We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function. RESULTS: Among 1,836 participants (mean age 40.7 ± 9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age 39.5 ± 9.5; 91.2% male). Among ever-smokers, 86% (n = 710) initiated smoking before deployment, while 11% (n = 90) initiated smoking during deployment(s). Smoking intensity was 50% greater during deployment than other periods (0.75 versus 0.50 packs-per-day; P < .05), and those with multiple deployments (40.4%) were more likely to smoke during deployment relative to those with single deployments (82% versus 74%). Total cumulative pack-years (median [IQR] = 3.8 [1, 10]) was inversely associated with post-bronchodilator FEV1%-predicted (-0.82; [95% CI] = [-1.25, -0.50] %-predicted per 4 pack-years) and FEV1/FVC%-predicted (-0.54; [95% CI] = [-0.78, -0.43] %-predicted per 4 pack-years). Deployment-related pack-years demonstrated similar point estimates of associations with FEV1%-predicted (-0.61; [95% CI] = [-2.28, 1.09]) and FEV1/FVC%-predicted (-1.09; [95% CI] = [-2.52, 0.50]) as non-deployment-related pack-years (-0.83; [95% CI] = [-1.26, -0.50] for FEV1%-predicted; -0.52; [95% CI] = [-0.73, -0.36] for FEV1/FVC%-predicted). CONCLUSIONS: Although cumulative pack-years smoking was modest in this cohort, an inverse association with pulmonary function was detectable. Deployment-related pack-years had a similar association with pulmonary function compared to non-deployment-related pack-years.

COVID-19 Severity and Mortality in Veterans with Chronic Lung Disease.

Rationale: Chronic lung diseases (CLDs) have been variably associated with a risk for more severe manifestations and death with coronavirus disease (COVID-19). Objectives: To determine the risk overall and by type of CLD for severity of COVID-19 outcomes in a U.S. national cohort. Methods: Using data from the Veterans Health Administration, we determined the risk associated with CLDs, including chronic obstructive pulmonary disease (COPD) (mild or severe), asthma (mild, active, or severe), idiopathic pulmonary fibrosis (IPF), sarcoidosis, and other interstitial lung diseases (ILDs) for outcomes among veterans with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive tests between March 1, 2020 and April 30, 2021. We used multinomial regression to estimate risk of four mutually exclusive COVID-19 outcomes within 30 days: outpatient management, hospitalization, hospitalization with indicators of critical illness, or death. We calculated the overall proportion with each outcome, the absolute risk difference, and risk ratios for each outcome between those with and without CLD. We also describe clinical and laboratory abnormalities by CLD in those hospitalized. Results: We included 208,283 veterans with COVID-19; 35,587 (17%) had CLD. Compared with no CLD, veterans with CLD were older and had more comorbidities. Hospitalized veterans with CLD were more likely to have low temperature, mean arterial pressure, oxygen saturation, and leukopenia and thrombocytopenia and were more likely to receive oxygen, mechanical ventilation, and vasopressors. Veterans with CLD were significantly less likely to have mild COVID-19 (-4.5%; adjusted risk ratio [aRR], 0.94; 95% confidence interval [CI], 0.94-0.95), and more likely to have a moderate (+2.5%; aRR, 1.21; 95% CI, 1.18-1.24), critical (+1.4%; aRR, 1.38; 95% CI, 1.32-1.45), or fatal (+0.7%; aRR, 1.15; 95% CI, 1.10-1.20) outcome. IPF was most strongly associated with COVID-19 severity, especially mortality (+3.2%; aRR, 1.69; 95% CI, 1.46-1.96), followed by other ILDs and COPD, whereas asthma was less likely to be associated with severity of COVID-19. In veterans younger than age 65 years, worse COVID-19 outcomes were generally more likely with IPF, sarcoidosis, and other ILDs. Conclusions: Veterans who had CLD, particularly IPF, other ILDs, and COPD, had an increased probability of more severe 30-day outcomes with COVID-19. These results provide insight into the absolute and relative risk of different CLDs with severity of COVID-19 outcomes and can help inform considerations of healthcare utilization and prognosis. Observational clinical epidemiology study registered with www.clinicaltrials.gov (NCT04628039).

Cognitive and Emotional Responses to Chronic Obstructive Pulmonary Disease Exacerbations and Patterns of Care Seeking.

Rationale: Cognitive and emotional responses associated with care seeking for chronic obstructive pulmonary disease (COPD) exacerbations are not well understood.Objectives: We sought to define care-seeking profiles based on whether and when U.S. veterans seek care for COPD exacerbations and compare cognitive and emotional responses with exacerbation symptoms across the profiles.Methods: This study analyzes data from a 1-year prospective observational cohort study of individuals with COPD. Cognitive and emotional responses to worsening symptoms were measured with the Response to Symptoms Questionnaire, adapted for COPD. Seeking care was defined as contacting or visiting a healthcare provider or going to the emergency department. Participants were categorized into four care-seeking profiles based on the greatest delay in care seeking for exacerbations when care was sought: 0-3 days (early), 4-7 days (short delay), >7 days (long delay), or never sought care for any exacerbation. The proportion of exacerbations for which participants reported cognitive and emotional responses was estimated for each care-seeking profile, stratified by the timing of when care was sought.Results: There were 1,052 exacerbations among 350 participants with Response to Symptoms Questionnaire responses. Participants were predominantly male (96%), and the mean age was 69.3 ± 7.2 years. For the 409 (39%) exacerbations for which care was sought, the median delay was 3 days. Those who sought care had significantly more severe COPD (forced expiratory volume in 1 s, modified Medical Research Council dyspnea scale) than those who never sought care. Regardless of the degree of delay until seeking care at one exacerbation, participants consistently reported experiencing serious symptoms if they sought care compared with events for which participants did not seek care (e.g., among early care seekers when care was sought, 36%; when care was not sought, 25%). Similar findings were seen in participants' assessment of the importance of getting care (e.g., among early care seekers when care was sought, 90%; when care was not sought, 52%) and their assessment of anxiety about the symptoms (e.g., among early care seekers when care was sought, 33%; when care was not sought, 17%).Conclusions: Delaying or not seeking care for COPD exacerbations was common. Regardless of care-seeking profile, cognitive and emotional responses to symptoms when care was sought differed from responses when care was not sought. Emotional and cognitive response to COPD exacerbations should be considered when developing individualized strategies to encourage seeking care for exacerbations.Clinical trial registered with www.clinicaltrials.gov (NCT02725294).

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.

Predictors of Patient-reported and Pharmacy Refill Measures of Maintenance Inhaler Adherence in Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Suboptimal adherence to inhaled medications in patients with chronic obstructive pulmonary disease (COPD) remains a challenge. Objectives: To examine the sociodemographic and clinical characteristics and medication beliefs associated with adherence measured by self-report and pharmacy data. Methods: A cross-sectional analysis of data from a prospective observational cohort study of patients with COPD was completed. Participants underwent spirometry and completed questionnaires regarding sociodemographic data, inhaler use, dyspnea, social support, psychological and medical comorbidities, and medication beliefs (Beliefs about Medicines Questionnaire [BMQ]). Self-reported adherence to inhaled medications was measured with the Adherence to Refills and Medications Scale (ARMS), and pharmacy-based adherence was calculated from administrative data using the ReComp score. Multivariable linear regression was used to examine the sociodemographic, clinical, and medication-belief factors associated with both adherence measures. Results: Among 269 participants with ARMS and ReComp data, adherence was the same for each measure (38.3%), but only 18% of participants were adherent by both measures. In multivariable adjusted analysis, a 10-year increase in age (ß = 0.54; 95% confidence interval, 0.14-0.94) and the number of maintenance inhalers used (ß = 0.53; 0.04-1.02) were associated with increased adherence by self-report. Improved ReComp adherence was associated with chronic prednisone use (ß = 0.18; 0.04-0.31) and the number of maintenance inhalers used (ß = 0.11; 0.05-0.17). In adjusted analyses examining patient beliefs about medications, increases in the COPD-specific BMQ concerns score (ß = -0.10; -0.17 to -0.02) were associated with reduced self-reported adherence. No significant associations between ReComp adherence and BMQ score were found in adjusted analyses. Conclusions: Adherence to inhaled COPD medications was poor as measured by self-report or pharmacy refill data. There were notable differences in factors associated with adherence based on the method of adherence measurement. Older age, chronic prednisone use, the number of prescribed maintenance inhalers used, and patient beliefs about medication safety were associated with adherence. Overall, fewer variables were associated with adherence as measured based on pharmacy refills. Pharmacy refill-based and self-reported adherence may measure distinct aspects of adherence and may be affected by different factors. These results also underscore the importance of addressing patient beliefs when developing interventions to improve medication adherence.

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.

Association between self-reported falling risk and risk of hospitalization for patients with chronic obstructive pulmonary disease.

RATIONALE: The association between self-report falling risk in persons with COPD and hospitalization has not been previously explored. OBJECTIVE: To examine whether self-reported risk is associated with hospitalizations in patients with COPD. METHODS: A secondary analysis from a prospective observational cohort study of veterans with COPD. Participants completed questions from the Stopping Elderly Accidents, Deaths and Injuries (STEADI) tool kit at either baseline or at the end of the 12-month study. A prospective or cross-sectional analysis examined the association between responses to the STEADI questions and risk of all-cause or COPD hospitalizations. RESULTS: Participants (N = 388) had a mean age of 69.6 ± 7.5 years, predominately male (96 %), and 144 (37.1 %) reported having fallen in the last year. More than half reported feeling unsteady with walking (52.6 %) or needing to use their arms to stand up from a chair (61.1 %). A third were concerned about falling (33.3 %). Three questions were associated with all-cause (not COPD) hospitalization in both unadjusted and adjusted cross-sectional analysis (N = 213): "fallen in the past year" (IRR 1.77, 95 % CI 1.10 to 2.86); "unsteady when walking" (IRR 1.88, 95 % CI 1.14 to 3.10); "advised to use a cane or walker" (IRR 1.89, 95 % CI 1.16 to 3.08). CONCLUSIONS: The prevalence of self-reported falling risk was high in this sample of veterans with COPD. The association between falling risk and all-cause hospitalization suggests that non-COPD hospitalizations can negatively impact intrinsic risk factors for falling. Further research is needed to clarify the effects of all-cause hospitalization on falling risk in persons with COPD.

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.

Care-seeking and delay of care during COPD exacerbations.

Patients who receive earlier treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) have a better prognosis, including earlier symptom resolution and reduced risk of future emergency-department visits (ED) or hospitalizations. However, many patients delay seeking care or do not report worsening symptoms to their healthcare provider. In this study, we aimed to understand how patients perceived their breathing symptoms and identify factors that led to seeking or delaying care for an acute exacerbation of COPD. We conducted semistructured interviews with 60 individuals following a recent COPD exacerbation. Participants were identified from a larger study of outpatients with COPD by purposive sampling by exacerbation type: 15 untreated, 15 treated with prednisone and/or antibiotics in the outpatient setting, 16 treated in an urgent care or ED setting, and 14 hospitalized. Data were analyzed using inductive content analysis. Participants were primarily male (97%) with a mean age of 69.1 ± 6.9 years, mean FEV1 1.42 (±0.63), and mean mMRC dyspnea of 2.7 (±1.1). We identified 4 primary themes: (i) access and attitudinal barriers contribute to reluctance to seek care, (ii) waiting is a typical response to new exacerbations, (iii) transitioning from waiting to care-seeking: the tipping point, and (iv) learning from and avoiding worse outcomes. Interventions to encourage earlier care-seeking for COPD exacerbations should consider individuals' existing self-management approaches, address attitudinal barriers to seeking care, and consider health-system changes to increase access to non-emergent outpatient treatment for exacerbations.Clinical Trial Registration NCT02725294.

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.

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.

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.

Development of COVIDVax Model to Estimate the Risk of SARS-CoV-2-Related Death Among 7.6 Million US Veterans for Use in Vaccination Prioritization.

Importance: A strategy that prioritizes individuals for SARS-CoV-2 vaccination according to their risk of SARS-CoV-2-related mortality would help minimize deaths during vaccine rollout. Objective: To develop a model that estimates the risk of SARS-CoV-2-related mortality among all enrollees of the US Department of Veterans Affairs (VA) health care system. Design, Setting, and Participants: This prognostic study used data from 7 635 064 individuals enrolled in the VA health care system as of May 21, 2020, to develop and internally validate a logistic regression model (COVIDVax) that predicted SARS-CoV-2-related death (n = 2422) during the observation period (May 21 to November 2, 2020) using baseline characteristics known to be associated with SARS-CoV-2-related mortality, extracted from the VA electronic health records (EHRs). The cohort was split into a training period (May 21 to September 30) and testing period (October 1 to November 2). Main Outcomes and Measures: SARS-CoV-2-related death, defined as death within 30 days of testing positive for SARS-CoV-2. VA EHR data streams were imported on a data integration platform to demonstrate that the model could be executed in real-time to produce dashboards with risk scores for all current VA enrollees. Results: Of 7 635 064 individuals, the mean (SD) age was 66.2 (13.8) years, and most were men (7 051 912 [92.4%]) and White individuals (4 887 338 [64.0%]), with 1 116 435 (14.6%) Black individuals and 399 634 (5.2%) Hispanic individuals. From a starting pool of 16 potential predictors, 10 were included in the final COVIDVax model, as follows: sex, age, race, ethnicity, body mass index, Charlson Comorbidity Index, diabetes, chronic kidney disease, congestive heart failure, and Care Assessment Need score. The model exhibited excellent discrimination with area under the receiver operating characteristic curve (AUROC) of 85.3% (95% CI, 84.6%-86.1%), superior to the AUROC of using age alone to stratify risk (72.6%; 95% CI, 71.6%-73.6%). Assuming vaccination is 90% effective at preventing SARS-CoV-2-related death, using this model to prioritize vaccination was estimated to prevent 63.5% of deaths that would occur by the time 50% of VA enrollees are vaccinated, significantly higher than the estimate for prioritizing vaccination based on age (45.6%) or the US Centers for Disease Control and Prevention phases of vaccine allocation (41.1%). Conclusions and Relevance: In this prognostic study of all VA enrollees, prioritizing vaccination based on the COVIDVax model was estimated to prevent a large proportion of deaths expected to occur during vaccine rollout before sufficient herd immunity is achieved.

BMI and Outcomes of SARS-CoV-2 Among US Veterans.

OBJECTIVE: The purpose of this study is to examine the associations of BMI with testing positive for severe acute respiratory coronavirus 2 (SARS-CoV-2) and risk of adverse outcomes in a cohort of Veterans Affairs enrollees. METHOD: Adjusted relative risks/hazard ratios (HRs) were calculated for the associations between BMI category (underweight, normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity) and testing positive for SARS-CoV-2 or experiencing hospitalization, intensive care unit admission, mechanical ventilation, and death among those testing positive. RESULTS: Higher BMI categories were associated with higher risk of a positive SARS-CoV-2 test compared with the normal weight category (class 3 obesity adjusted relative risk: 1.34, 95% CI: 1.28-1.42). Among 25,952 patients who tested positive for SARS-CoV-2, class 3 obesity was associated with higher risk of mechanical ventilation (adjusted HR [aHR]: 1.77, 95% CI: 1.35-2.32) and mortality (aHR: 1.42, 95% CI: 1.12-1.78) compared with normal weight individuals. These associations were present primarily in patients younger than 65 and were attenuated or absent in older age groups (interaction P < 0.05). CONCLUSION: Veterans Affairs enrollees with higher BMI were more likely to test positive for SARS-CoV-2 and were more likely to be mechanically ventilated or die if infected with SARS-CoV-2. Higher BMI contributed relatively more to the risk of death in those younger than 65 years of age as compared with other age categories.

Serotonin transporter gene polymorphisms and depressive symptoms in patients with chronic obstructive pulmonary disease.

Background: We examined the relationship between polymorphisms in the promoter region of the serotonin transport (SERT) gene (5-HTTLPR, short 'S' and long 'L' alleles) and in intron 2 variable number tandem repeat (STin2VNTR, 9, 10, or 12-repeat alleles) with depression or anxiety in patients with COPD.Methods: 302 patients with moderate to severe COPD participated in SERT study. History and number of prior depressive episodes were measured using the Structured Clinical Interview for Depression; Hospital Anxiety Depression Scale (HAD) depression ≥8 or a Patient Health Questionnaire-9 (PHQ-9) >,10.Results: 240 (80%) male sample had a mean age of 68.0 years. Current depression was 22% (HAD) or 21% (PHQ-9), anxiety was 25% (HAD), and suicidal ideation (6%). 5-HTTLPR or STin2 VNTR genotypes were not associated with current depressive or anxiety symptoms. The mean number of prior depressive episodes was higher for patients with the 5-HTTLPR genotype S/S or S/L compared with L/L (4.4 ± 6.1; 5.3 ± 6.8; 4.0 ± 6.1, p < 0.001) and with STin2VNTR high-risk genotype (9/12 or 12/12), medium risk (9/10 or 10/12) compared to low risk (10/10) genotypes (5.1 ± 6.8; 4.9 ± 6.7; 2.7 ± 4.5, p < 0.001).Conclusions: SERT 5-HTTLPR and STin2-VNTR polymorphisms were not associated with current depressive and anxiety symptoms, but the high-risk STin2-VNTR genotypes and S/L were associated with the number of prior depressive episodes.

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.