Elevated Pulmonary Arterial Compliance Is Associated with Survival in Pulmonary Hypertension: Results from a Novel Network Medicine Analysis.

Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U.S. Veterans Affairs system (October 1, 2006-September 30, 2018). Network medicine framework was used to subgroup patients when considering an N of 79 variables per patient. The results informed outcome analyses in the discovery cohort and a sex-balanced validation right heart catheterization cohort from Vanderbilt University (September 24, 1998-December 20, 2013). Measurements and Main Results: From an N of 4,737 complete case patients with mPAP of 19-24 mm Hg, there were 21 distinct subgroups (network modules) (all-cause mortality range = 15.9-61.2% per module). Pulmonary arterial compliance (PAC) drove patient assignment to modules characterized by increased survival. When modeled continuously in patients with mPAP ⩾19 mm Hg (N = 37,744; age, 67.2 yr [range = 61.7-73.8 yr]; 96.7% male; median follow-up time, 1,236 d [range = 570-1,971 d]), the adjusted all-cause mortality hazard ratio was <1.0 beginning at PAC ⩾3.0 ml/mm Hg and decreased progressively to ∼7 ml/mm Hg. A protective association between PAC ⩾3.0 ml/mm Hg and mortality was also observed in the validation cohort (N = 1,514; age, 60.2 yr [range = 49.2-69.1 yr]; 48.0% male; median follow-up time, 2,485 d [range = 671-3,580 d]). The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P < 0.001) and 49% (95% confidence interval, 0.38-0.69; P < 0.001) improvements in survival were observed for PAC ⩾3.0 versus <3.0 ml/mm Hg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC ⩾3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.

Conducting health services research during the COVID-19 pandemic: experiences from the veterans health administration.

BACKGROUND: Health services researchers within the Veterans Health Administration (VA) seek to improve the delivery of care to the Veteran population, whose medical needs often differ from the general population. The COVID-19 pandemic and restricted access to medical centers and offices forced VA researchers and staff to transition to remote work. This study aimed to characterize the work experience of health service researchers during the COVID-19 pandemic. METHODS: A REDCap survey developed from the management literature was distributed in July 2020 to 800 HSR&D researchers and staff affiliated with VA Centers of Innovation. We requested recipients to forward the survey to VA colleagues. Descriptive analyses and logistic regression modeling were conducted on multiple choice and Likert scaled items. Manifest content analysis was conducted on open-text responses. RESULTS: Responses were received from 473 researchers and staff from 37 VA Medical Centers. About half (48%; n = 228) of VA HSR&D researchers and staff who responded to the survey experienced some interference with their research due to the COVID-19 pandemic, yet 55% (n = 260) reported their programs of research did not slow or stop. Clinician investigators reported significantly greater odds of interference than non-clinician investigators and support staff. The most common barriers to working remotely were loss of face-to-face interactions with colleagues (56%; n = 263) and absence of daily routines (25%; n = 118). Strategies teams used to address COVID-19 related remote work challenges included videoconferencing (79%; n = 375), virtual get-togethers (48%; n = 225), altered timelines (42%; n = 199), daily email updates (30%; n = 143) and virtual team huddles (16%; n = 74). Pre-pandemic VA information technology structures along with systems created to support multidisciplinary research teams working across a national healthcare system maintained and enhanced staff engagement and well-being. CONCLUSIONS: This study identifies how the VA structures and systems put in place prior to the COVID-19 pandemic to support a dispersed workforce enabled the continuation of vital scientific research, staff engagement and well-being during a global pandemic. These findings can inform remote work policies and practices for researchers during the current and future crises.

Impact of severity of baseline thrombocytopenia on outcomes after percutaneous coronary interventions: Analysis from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program.

OBJECTIVES: The aim of this study was to evaluate the effect of the degree of severity of baseline thrombocytopenia (TCP) on outcomes after percutaneous coronary intervention (PCI) BACKGROUND: The association of TCP with clinical outcomes among patients undergoing coronary intervention has not been previously evaluated. METHODS: Using data from the US Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program, we identified patients undergoing PCI between October 1, 2007, to September 30, 2017. The cohort was then stratified by platelet count, as no TCP (platelet count >150,000/mcl), mild TCP (100-150,000/mcl), or moderate-severe TCP (<100,000/mcl) and this was associated with clinical outcomes. RESULTS: The cohort included 80,427 patients (98% male), of which 14.9% (13.2% mild, 1.7% moderate-severe) suffered from TCP at the time of PCI. Compared with mild or no TCP, moderate-severe TCP was associated with increased risk of post-PCI pericardiocentesis (0.6% vs. 0.2% vs. 0.2%, p = 0.018) and in-hospital mortality (1.5% vs. 0.7% vs. 0.7%) without a difference in postprocedure stroke (0.5% vs. 0.3% vs. 0.3%, p = 0.6). Over a median follow-up of 1729 days, time-to-repeat revascularization was significantly shorter in moderate-severe TCP (1080 vs. 1347 vs. 1467 days, p < 0.001) despite lower risk of revascularization. Both mild (adjusted HR: 1.11, 95% CI: 1.07-1.15, p < 0.001) and moderate-severe TCP (HR: 1.55, 95% CI: 1.43-1.69, p < 0.001) were associated with increased all-cause mortality compared with those without TCP. CONCLUSIONS: Thrombocytopenia was associated with increased short- and long-term adverse events among patients undergoing PCI. Any degree of TCP was associated with increased long-term all-cause mortality while moderate-severe TCP was also associated with increased risk of periprocedural adverse events.

Depression and long-term prognostic outcomes following peripheral endovascular interventions in the VA Healthcare System.

The association between depression and peripheral artery disease (PAD) outcomes remains widely understudied. In patients with PAD undergoing a peripheral vascular intervention (PVI) who have a recent diagnosis of depression, it is unknown what their long-term outcomes are and what factors may mediate an adverse risk. We therefore studied 797 consecutive patients undergoing PVI across 33 Veterans Affairs (VA) centers. Depression and outcomes were documented from patients' medical records. Outcomes included: (1) all-cause death; (2) non-fatal cardiovascular events (myocardial infarction, stroke); and (3) PAD-related events (including repeat PVI or amputation). Cox proportional hazards frailty models were constructed, adjusting for age. Additional covariates were selected if they resulted in at least 5% change in the age-adjusted hazard ratio (HR) for depression on outcomes. Overall, 265 (33%) patients had a diagnosis of depression. After a median follow-up of 955 days (range 1-6.25 years), 52 (6.5%) patients died, 30 (3.8%) experienced non-fatal cardiovascular events, and 176 (22.1%) had PAD-related events. Compared to patients without depression, depressed patients had higher rates of non-fatal cardiovascular events (6.4% vs 2.4%, p-value 0.0055). No differences for the other outcomes were noted. Higher risk for non-fatal cardiovascular events persisted after adjustment for age (HR 1.6, 95% CI 1.05-2.47). The only additional covariate that met our selection criteria was hypertension. After adjusting for hypertension, the association between depression and non-fatal cardiovascular outcomes attenuated (HR 1.53, 95% CI 0.99-2.35). In conclusion, a diagnosis of depression in veterans undergoing PVI was associated with increased risk of non-fatal cardiovascular events, mediated by age and hypertension.

Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

BACKGROUND: Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. METHODS AND RESULTS: We analyzed retrospectively all US veterans undergoing right heart catheterization (2007-2012) in the Veterans Affairs healthcare system (n=21,727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004-1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (≤18 mm Hg; n=4,207); (2) borderline PH (19-24 mm Hg; n=5,030); and (3) PH (≥25 mm Hg; n=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12-1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96-2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01-1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09-1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. CONCLUSIONS: These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.

A randomized controlled trial of a community-based dementia care coordination intervention: effects of MIND at Home on caregiver outcomes.

OBJECTIVE: To assess whether MIND at Home, a community-based, multicomponent, care coordination intervention, reduces unmet caregiving needs and burden in informal caregivers of persons with memory disorders. METHODS: An 18-month randomized controlled trial of 289 community-living care recipient (CR)-caregiver (informal caregivers, i.e., unpaid individuals who regularly assisted the CR) dyads from 28 postal code areas of Baltimore, Maryland was conducted. All dyads and the CR's primary care physician received the written needs assessment results and intervention recommendations. Intervention dyads then received an 18-month care coordination intervention delivered by nonclinical community workers to address unmet care needs through individualized care planning, referral and linkage to dementia services, provision of caregiver dementia education and skill-building strategies, and care progress monitoring by an interdisciplinary team. Primary outcome was total percent of unmet caregiver needs at 18 months. Secondary outcomes included objective and subjective caregiver burden measures, quality of life (QOL), and depression. RESULTS: Total percent of unmet caregiver needs declined in both groups from baseline to 18 months, with no statistically significant between-group difference. No significant group differences occurred in most caregiver burden measures, depression, or QOL. There was a potentially clinically relevant reduction in self-reported number of hours caregivers spent with the CR for MIND participants compared with control subjects. CONCLUSION: No statistically significant impacts on caregiver outcomes were found after multiple comparison adjustments. However, MIND at Home appeared to have had a modest and clinically meaningful impact on informal caregiver time spent with CRs.

Family history, not lack of medication use, is associated with the development of postpartum depression in a high-risk sample.

We sought to determine clinical predictors of postpartum depression (PPD), including the role of medication, in a sample of women followed prospectively during and after pregnancy. Women with a history of mood disorder were recruited and evaluated during each trimester and 1 week, 1 month, and 3 months postpartum. DSM-IV criteria for a major depressive episode were assessed by a psychiatric interview at each time point. Sixty-three women with major depression and 30 women with bipolar disorder entered the study and 75.4 % met DSM-IV criteria for a MDE during pregnancy, postpartum, or both. We modeled depression in a given time period (second trimester, third trimester, or 1 month postpartum) as a function of medication use during the preceding period (first, second, or third trimester). The odds of being depressed for those who did not use medication in the previous period was approximately 2.8 times that of those who used medication (OR 2.79, 95 % CI 1.38-5.66, p = 0.0048). Of 38 subjects who were psychiatrically well during the third trimester, 39.5 % (N = 15) met the criteria for a MDE by 4 weeks postpartum. In women who developed PPD, there was a high rate of a family history of PPD (53.3 %) compared to women who did not develop PPD (11.8 %, p = 0.02). While the use of psychiatric medications during pregnancy reduced the odds of being depressed overall, the use of psychiatric medications during pregnancy may not protect against PPD in women at high risk, particularly those with a family history of PPD.

Correlates of quality of life for individuals with dementia living at home: the role of home environment, caregiver, and patient-related characteristics.

OBJECTIVES: To examine prevalence of modifiable risk factors and their contribution to patient quality of life (QoL) as rated by dementia patients and family caregivers. DESIGN: Cross-sectional. SETTING: Home environment. PARTICIPANTS: 88 patients and their caregivers. MEASUREMENTS: Modifiable characteristics of home environments, patients, and caregivers were observed or obtained through interview. Demographics and ratings of patients' QoL were obtained from patients and caregivers. RESULTS: Patients had mean Mini-mental Status Examination (MMSE) score = 17.7 ± 4.6, (range: 10-28) on an average 7.7 ± 2.4 neuropsychiatric behaviors, 6.0 ± 3.1 health conditions and moderate functional challenges; 70.7% (N = 58) had fall risk; 60.5% (N = 52) had sleep problems at least once weekly; and 42.5% (N = 37) had pain. An average of 8.1 ± 5.2 home hazards and 5.4 ± 4.1 adaptations were observed; 51.7% had unmet device/navigation needs. Patients' and caregivers' QoL ratings were unrelated to MMSE; and patients' self-rated QoL was higher than rated by caregivers. Number of health conditions and unmet device/navigation needs were inversely associated with patient self-rated QoL, and number of health conditions, frequency of behaviors, and level of negative communications were inversely associated with caregiver's assessment of patient QoL. Positive endorsement of caregiving was positively associated with caregiver's appraisal of patient QoL. Other factors were unrelated. CONCLUSIONS: Most patients lived at home with high fall risk, unmanaged behavioral symptoms, pain, sleep disturbances, environmental challenges, and multiple hazards. Except for health, factors associated with lower QoL differed for patients and caregivers. Results suggest need to improve QoL by addressing modifiable risk factors and tailoring interventions to patient and caregiver perspectives.

A multidimensional home-based care coordination intervention for elders with memory disorders: the maximizing independence at home (MIND) pilot randomized trial.

OBJECTIVES: To assess whether a dementia care coordination intervention delays time to transition from home and reduces unmet needs in elders with memory disorders. DESIGN: 18-month randomized controlled trial of 303 community-living elders. SETTING: 28 postal code areas of Baltimore, MD. PARTICIPANTS: Age 70+ years, with a cognitive disorder, community-living, English-speaking, and having a study partner available. INTERVENTION: 18-month care coordination intervention to systematically identify and address dementia-related care needs through individualized care planning; referral and linkage to services; provision of dementia education and skill-building strategies; and care monitoring by an interdisciplinary team. MEASUREMENTS: Primary outcomes were time to transfer from home and total percent of unmet care needs at 18 months. RESULTS: Intervention participants had a significant delay in time to all-cause transition from home and the adjusted hazard of leaving the home was decreased by 37% (Hazard ratio: 0.63, 95% Confidence Interval: 0.42-0.94) compared with control participants. Although there was no significant group difference in reduction of total percent of unmet needs from baseline to 18 months, the intervention group had significant reductions in the proportion of unmet needs in safety and legal/advance care domains relative to controls. Intervention participants had a significant improvement in self-reported quality of life (QOL) relative to control participants. No group differences were found in proxy-rated QOL, neuropsychiatric symptoms, or depression. CONCLUSIONS: A home-based dementia care coordination intervention delivered by non-clinical community workers trained and overseen by geriatric clinicians led to delays in transition from home, reduced unmet needs, and improved self-reported QOL.

A home-based intervention to reduce depressive symptoms and improve quality of life in older African Americans: a randomized trial.

BACKGROUND: Effective care models for treating older African Americans with depressive symptoms are needed. OBJECTIVE: To determine whether a home-based intervention alleviates depressive symptoms and improves quality of life in older African Americans. DESIGN: Parallel, randomized trial stratified by recruitment site. Interviewers assessing outcomes were blinded to treatment assignment. (ClinicalTrials.gov: NCT00511680). SETTING: A senior center and participants' homes from 2008 to 2010. PATIENTS: African Americans aged 55 years or older with depressive symptoms. INTERVENTION: A multicomponent, home-based intervention delivered by social workers or a wait-list control group that received the intervention at 4 months. MEASUREMENTS: Self-reported depression severity at 4 months (primary outcome) and depression knowledge, quality of life, behavioral activation, anxiety, function, and remission at 4 and 8 months. RESULTS: Of 208 participants (106 and 102 in the intervention and wait-list groups, respectively), 182 (89 and 93, respectively) completed 4 months and 160 (79 and 81, respectively) completed 8 months. At 4 months, participants in the intervention group showed reduced depression severity (difference in mean change in Patient Health Questionnaire-9 score from baseline, -2.9 [95% CI, -4.6 to -1.2]; difference in mean change in Center for Epidemiologic Studies Depression Scale score from baseline, -3.7 [CI, -5.4 to -2.1]); improved depression knowledge, quality of life, behavioral activation, and anxiety (P < 0.001); and improved function (P = 0.014) compared with wait-list participants. More intervention than wait-list participants entered remission at 4 months (43.8% vs. 26.9%). After treatment, control participants showed benefits similar in magnitude to those of participants in the initial intervention group. Those in the initial intervention group maintained benefits at 8 months. LIMITATION: The study had a small sample, short duration, and differential withdrawal rate. CONCLUSION: A home-based intervention delivered by social workers could reduce depressive symptoms and enhance quality of life in most older African Americans. PRIMARY FUNDING SOURCE: National Institute of Mental Health.

Developing a relational playbook for cardiology teams to cultivate supportive learning environments, enhance clinician well-being, and veteran care.

Introduction: Despite the Veterans Health Administration (VA) efforts to become a learning health system (LHS) and high-reliability organization (HRO), interventions to build supportive learning environments within teams are not reliably implemented, contributing to high levels of burnout, turnover, and variation in care. Supportive learning environments build capabilities for teaching and learning, empower teams to safely trial and adapt new things, and adopt highly reliable work practices (eg, debriefs). Innovative approaches to create supportive learning environments are needed to advance LHS and HRO theory and research into practice. Methods: To guide the identification of evidence-based interventions that cultivate supportive learning environments, the authors used a longitudinal, mixed-methods design and LHS and HRO frameworks. We partnered with the 81 VA cardiac catheterization laboratories and conducted surveys, interviews, and literature reviews that informed a Relational Playbook for Cardiology Teams. Results: The Relational Playbook resources and 50 evidence-based interventions are organized into five LHS and HRO-guided chapters: Create a positive culture, teamwork, leading teams, joy in work, communication, and high reliability. The interventions are designed for managers to integrate into existing meetings or trainings to cultivate supportive learning environments. Conclusions: LHS and HRO frameworks describe how organizations can continually learn and deliver nearly error-free services. The Playbook resources and interventions translate LHS and HRO frameworks for real-world implementation by healthcare managers. This work will cultivate supportive learning environments, employee well-being, and Veteran safety while providing insights into LHS and HRO theory, research, and practice.

Comparison of three societally derived health-state classification values among older African Americans with depressive symptoms.

PURPOSE: To compare societal values across three health-state classification systems in older African Americans with depression and to describe the association of these instruments to depression severity. METHODS: We summarized baseline values for EQ-5D (US weights) and HUI2/3 (Canadian weights) and their subscales for 118 older African American participants enrolled in a randomized depression treatment trial and calculated correlations between the different instruments. We evaluated ceiling and floor effects for each instrument by comparing the proportion at the highest and lowest possible score for each tool. Also, utility scores were assessed by level of depression severity (mild, moderate, moderate severe, severe) scores as measured by the Patient Health Questionnaire (PHQ-9). RESULTS: Mean utility values were 0.58 (SD = 0.21) for EQ-5D, 0.52 (SD = 0.21) for HUI2, and 0.36 (SD = 0.31) for HUI3. For the EQ-5D, 72 % of participants reported having some problems on the anxiety/depression domain. On the emotion domain for the HUI2, 23 % reported the highest level of impairment compared to only 3 % on the HUI3. No participant scored at the floor for the EQ-5D, HUI2, or HUI3 index; one participant scored at the ceiling value on the HUI3 index. Correlations ranged from 0.63 to 0.82 (all of which were significant at an alpha level of 0.05). In general, utility scores trended inversely with depression level. CONCLUSION: Small differences in the three preference-weighted health-state classification systems were evident for this sample of older African Americans with depressive symptoms, with HUI scores lower than EQ-5D. For this sample, utility scores were lower (i.e., poorer) than the general United States population with depression on each utility measure.

Learning environments, reliability enhancing work practices, employee engagement, and safety climate in VA cardiac catheterization laboratories.

OBJECTIVE: To characterize the relationship between learning environments (the educational approaches, cultural context, and settings in which teaching and learning happen) and reliability enhancing work practices (hiring, training, decision making) with employee engagement, retention, and safety climate. DATA SOURCE: We collected data using the Learning Environment and High Reliability Practices Survey (LEHRs) from 231 physicians, nurses, and technicians at 67 Veterans Affairs cardiac catheterization laboratories who care for high-risk Veterans. STUDY DESIGN: The association between the average LEHRs score and employee job satisfaction, burnout, intent to leave, turnover, and safety climate were modeled in separate linear mixed effect models adjusting for other covariates. DATA COLLECTION: Participants responded to a web-only survey from August through September 2020. PRINCIPAL FINDINGS: There was a significant association between higher average LEHRs scores and (1) higher job satisfaction (2) lower burnout, (3) lower intent to leave, (4) lower cath lab turnover in the previous 12 months, and (5) higher perceived safety climate. CONCLUSIONS: Learning environments and use of reliability enhancing work practices are potential new avenues to support satisfaction and safety climate while lowering burnout, intent to leave, and turnover in a diverse US health care workforce that serves a vulnerable and marginalized population.

A pilot study to assess the learning environment and use of reliability enhancing work practices in VHA cardiac catheterization laboratories.

INTRODUCTION: A learning health system (LHS) harnesses data and analytics to learn from clinical encounters to implement the best care with high reliability. The 81 Veterans Health Administration (VHA) cardiac catheterization laboratories (cath lab) are a model LHS. The quality and safety of coronary procedures are monitored and reported by the Clinical Assessment, Reporting and Tracking (CART) Program, which has identified variation in care across cath labs. This variation may be due to underappreciated aspects of LHSs, the learning environment and reliability enhancing work practices (REWPs). Learning environments are the educational approaches, context, and settings in which learning occurs. REWPs are the organizational practices found in high reliability organizations. High learning environments and use of REWPs are associated with improved outcomes. This study assessed the learning environments and use of REWPs in VHA cath labs to examine factors supportive of learning and high reliability. METHODS: In 2018, the learning organization survey-27 and the REWP survey were administered to 732 cath lab staff. Factor analysis and linear models were computed. Unit-level analyses and site ranking (high, low) were conducted on cath labs with >40% response rate using Bayesian methods. RESULTS: Surveys from 40% of cath lab staff (n = 294) at 84% of cath labs (n = 68) were included. Learning environment and REWP strengths across cath labs include the presence of training programs, openness to new ideas, and respectful interaction. Learning environment and REWP gaps include lack of structured knowledge transfer (eg, checklists) and low use of forums for improvement. Survey dimensions matched established factor structures and demonstrated high reliability (Cronbach's alpha >.76). Unit-level analyses were conducted for 29 cath labs. One ranked as high and four as low learning environments. CONCLUSIONS: This work demonstrates an approach to assess local learning environments and use of REWPs, providing insights for systems working to become a LHS.

Two Factor Structures Possible for the FACIT-Sp in Patients With Heart Failure.

CONTEXT: The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp) is a 12-item measure of spiritual well-being in chronic illness originally developed in patients with cancer. The overall scale, a two-factor model (meaning/peace, faith), and a three-factor model (meaning, peace, faith) have been proposed for the FACIT-Sp, and consensus on the best factor structure has not been reached. In addition, the factor structure of the FACIT-Sp has not been considered in patients with heart failure. OBJECTIVES: To examine the factor structure of the FACIT-Sp in heart failure patients. METHODS: A confirmatory factor analysis framework was used to test three competing models on 217 patients with heart failure using data from the CASA (Collaborative Care to Alleviate Symptoms and Adjust to Illness) trial. The overall scale (single factor), two-factor, and three-factor models were tested using baseline data, then confirmed with 12-month data. Model modifications were made based on empirical inspection of baseline data and replicated using 12-month data. Cronbach's alpha and correlations with measures of quality of life and psychological health were examined. RESULTS: All three models had strong factor loadings on all items except the negatively worded items. The two-factor and three-factor models fit reasonably well after modifications, but the single factor did not fit well (1/2/3-factor: RMSEA 0.14/0.09/0.06, CFI 0.85/0.93/0.97, SRMR 0.09/0.05/0.04). Internal consistency was sufficient for all factors. CONCLUSION: The two-factor and three-factor models were supported in heart failure patients. The three-factor model demonstrated better statistical fit but was not more interpretable. KEY MESSAGE: This study investigated the factor structure of the FACIT-Sp in patients with heart failure. The two-factor and three-factor models were supported, but the single factor model was not. Negatively worded items did not perform well.

Renin-Angiotensin-Aldosterone System Inhibitor Use and Mortality in Pulmonary Hypertension: Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking Database.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) contributes to pulmonary hypertension (PH) pathogenesis. Although animal data suggest that RAAS inhibition attenuates PH, it is unknown if RAAS inhibition is beneficial in PH patients. RESEARCH QUESTION: Is RAAS inhibitor use associated with lower mortality in a large cohort of patients with hemodynamically confirmed PH? STUDY DESIGN AND METHODS: We used the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Database to study retrospectively relationships between RAAS inhibitors (angiotensin converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], and aldosterone antagonists [AAs]) and mortality in 24,221 patients with hemodynamically confirmed PH. We evaluated relationships in the full and in propensity-matched cohorts. Analyses were adjusted for demographics, socioeconomic status, comorbidities, disease severity, and comedication use in staged models. RESULTS: ACEI and ARB use was associated with improved survival in unadjusted Kaplan-Meier survival analyses in the full cohort and the propensity-matched cohort. This relationship was insensitive to adjustment, independent of pulmonary artery wedge pressure, and also was observed in a cohort restricted to individuals with precapillary PH. AA use was associated with worse survival in unadjusted Kaplan-Meier survival analyses in the full cohort; however, AA use was associated less robustly with mortality in the propensity-matched cohort and was not associated with worse survival after adjustment for disease severity, indicating that AAs in real-world practice are used preferentially in sicker patients and that the unadjusted association with increased mortality may be an artifice of confounding by indication of severity. INTERPRETATION: ACEI and ARB use is associated with lower mortality in veterans with PH. AA use is a marker of disease severity in PH. ACEIs and ARBs may represent a novel treatment strategy for diverse PH phenotypes.

Alcohol use disorders affect antimicrobial proteins and anti-pneumococcal activity in epithelial lining fluid obtained via bronchoalveolar lavage.

AIMS: Our overall objective was to examine whether characteristics of epithelial lining fluid (ELF) from subjects with alcohol use disorders (AUDs) obtained via bronchoalveolar lavage (BAL) contribute to their predisposition to pneumococcal pneumonia. We sought to compare the anti-pneumococcal activity of acellular human BAL from subjects with AUDs to matched controls. Further, differences in BAL lysozyme activity and lactoferrin concentrations between these two groups were examined to determine the effect of AUDs on these antimicrobial proteins. METHODS: BAL was performed in subjects with AUDs and matched controls. Acellular BAL was used at varying concentrations in an in vitro killing assay of Streptococcus pneumoniae, type 2, and the percent kill of organisms per microgram per milliliter total BAL protein was ascertained. Lysozyme activity and lactoferrin concentrations were measured in BAL from subjects and controls at measured concentrations of BAL protein. RESULTS: AUD subjects (n = 15) and controls (n = 10) were enrolled in these investigations who were balanced in terms of smoking history. Using a mixed effect model, across the range of BAL protein concentrations, killing of pneumococcus tended to be less potent with BAL fluid from AUD subjects. Additionally, lysozyme activity and lactoferrin concentrations were significantly lower in the AUD group. CONCLUSIONS: The predisposition for pneumococcal pneumonia among those with AUDs may be in part mediated through effects of alcohol on substances within ELF that include antimicrobial proteins. Clarifying the composition and activity of ELF antimicrobial proteins in the setting of AUDs via investigations with human BAL fluid can help establish their contribution to the susceptibility for pulmonary infections in these individuals.

Long-term predictive value of stroke volume index obtained from right heart catheterization: Insights from the veterans affairs clinical assessment, reporting, and tracking program.

BACKGROUND: Right heart catheterization-derived hemodynamic parameters have been associated with short-term prognosis. HYPOTHESIS: Hemodynamic parameters will be associated with long-term prognosis. METHODS: Retrospective cohort study from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program included patients who underwent an index right heart catheterization between 2008 and 2016. Cox proportional hazard models were used to examine the association between stroke volume index and all-cause mortality. RESULTS: For the final cohort of 37 209 patients, mean follow-up was 3.7 ± 2.5 years. All-cause mortality was 42.0% in the low (<35 cc/beat/m2 ) compared with 33.2% in the normal stroke volume index group (≥35 cc/beat/m2 ). In adjusted analysis, low stroke volume was significantly associated with higher mortality risk (HR (95% CI) 1.14 (1.10-1.18); P < .001) independent of clinical parameters. The area under the curve (AUC) for continuous measures of stroke volume index at predicting mortality in a Cox proportional hazard model was 0.56 at 3 years. When stroke volume index was combined with 14 clinical covariates, the AUC was 0.70 at 3 years. The addition of stroke volume index to these clinical covariates did not increase the discriminatory ability of the model at 1 year in a clinically meaningful way (integrated discrimination improvement index = 0.0021, 95% CI: 0.0010-0.0034). CONCLUSIONS: The long-term prognostic value of right heart catheterization-derived stroke volume index appears to be marginal. While there was a weak association of low stroke volume index and excess mortality, inclusion of this parameter to a set of clinical covariates did not improve prognostic discrimination.