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1.  Assessment and Management of Symptoms for Outpatients Newly Diagnosed with Lung Cancer 
Rationale
Little is known about symptom assessment around the time of lung cancer diagnosis. The purpose of this pilot study was to assess symptoms within 2 months of diagnosis and the frequency with which clinicians addressed symptoms among a cohort of Veterans (n=20) newly diagnosed with lung cancer. We administered questionnaires then reviewed medical records to identify symptom assessment and management provided by subspecialty clinics for 6 months following diagnosis.
Results
Half of patients (50%) were diagnosed with early stage non-small cell lung cancer (NSCLC), stage I or II. At baseline, 45% patients rated their overall symptoms severe. There were no significant differences in symptoms among patients with early or late stage NSCLC or small cell lung cancer. Of the 212 clinic visits over 6 months, 70.2% occurred in oncology. Clinicians most frequently addressed pain, although assessment differed by clinic.
Conclusions
Veterans with newly diagnosed lung cancer report significant symptom burden. Despite ample opportunities to address patients’ symptoms, variations in assessment exist among subspecialty services. Coordinated approaches to symptom assessment are likely needed among patients newly diagnosed with lung cancer.
doi:10.1177/1049909114557635
PMCID: PMC4459914  PMID: 25376224
lung cancer; newly diagnosed; symptom assessment; management
2.  Distress and Patient-Centered Communication among Veterans with Incidental (Not Screen-Detected) Pulmonary Nodules. A Cohort Study 
Rationale: Incidental pulmonary nodule detection is postulated to cause distress, but the frequency and magnitude of that distress have not been reported. The quality of patient–clinician communication and the perceived risk of lung cancer may influence distress
Objectives: To evaluate the association of communication processes with distress and the perceived risk of lung cancer using validated instruments.
Methods: We conducted a prospective cohort study of patients with incidentally detected nodules who received care at one Department of Veterans Affairs Medical Center. We measured distress with the Impact of Event Scale and patient-centered communication with the Consultation Care Measure, both validated instruments. Risk of lung cancer was self-reported by participants. We used multivariable adjusted logistic regression to measure the association of communication quality with distress.
Measurements and Main Results: Among 122 Veterans with incidental nodules, 23%, 12%, and 4% reported experiencing mild, moderate, and severe distress, respectively, at the time they were informed of the pulmonary nodule. Participant-reported risk of lung cancer was not associated with distress. In the adjusted model, high-quality communication was associated with decreased distress (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.08–1.00, P = 0.05). Among participants who reported a risk of malignancy of 30% or less, high-quality communication was associated with decreased distress (OR = 0.15, 95% CI = 0.02–0.92, P = 0.04), but was not associated with distress for those who reported a risk greater than 30% (OR = 0.12 (95% CI = 0.00–3.97, P = 0.24), although the P value for interaction was not significant.
Conclusions: Veterans with incidental pulmonary nodules frequently reported inadequate information exchange regarding their nodule. Many patients experience distress after they are informed that they have a pulmonary nodule, and high-quality patient–clinician communication is associated with decreased distress. Communication strategies that only target improved knowledge of the risk of malignancy may not be sufficient to reduce the distress associated with nodule detection.
doi:10.1513/AnnalsATS.201406-283OC
PMCID: PMC4342836  PMID: 25521482
pulmonary nodule; patient-clinician communication; patient-centered outcomes
3.  The Influence of Hospitalization or Intensive Care Unit Admission on Declines in Health-Related Quality of Life 
Rationale: Survivors of critical illness report impaired health-related quality of life (HRQoL) after hospital discharge, but the degree to which these impairments are attributable to critical illness is unknown.
Objectives: We sought to examine changes in HRQoL associated with an intensive care unit (ICU) stay and the differential association of type of hospitalization (critical illness versus noncritical illness) on changes in HRQoL.
Methods: We identified 11,243 participants in the Ambulatory Care Quality Improvement Project (a multicenter randomized trial of Veterans conducted March 1997 to August 2000) completing at least two Medical Outcomes Study Short-Form 36 questionnaires over 2 years, and categorized patients by hospitalization status during the interval between measures. We used multiple linear regression with generalized estimating equations for analysis.
Measurements and Main Results: Our primary outcome was change in the Physical Component Summary score. Participants requiring hospitalization or ICU admission had significantly worse baseline HRQoL than those not hospitalized (P < 0.001). Compared with patients who were not hospitalized, follow-up Physical Component Summary scores were lower among non-ICU hospitalized patients and ICU patients (adjusted β-coefficient = −1.40 [95% confidence interval, −1.81, −0.99] and adjusted β-coefficient = −1.53 [95% confidence interval, −2.11, −0.95], respectively), with no difference between the two groups (P value = 0.80). Similar results were seen for the Mental Component Summary score and each of the Medical Outcomes Study Short-Form 36 subdomains.
Conclusions: Prehospital HRQoL is a significant determinant of HRQoL after hospitalization or ICU admission. Hospitalization is associated with increased risk of impairment in HRQoL after discharge, yet the overall magnitude of this reduction is small and similar between non-ICU hospitalized and critically ill patients.
doi:10.1513/AnnalsATS.201404-172OC
PMCID: PMC4342801  PMID: 25493656
quality of life; critical illness; intensive care units; cohort studies; outcome assessment (health care)
4.  Predictors of Imaging Surveillance for Surgically Treated, Early-Stage Lung Cancer 
The Annals of thoracic surgery  2014;98(6):1944-1952.
Background
Current guidelines recommend routine imaging surveillance for non-small cell lung cancer (NSCLC) patients following treatment. Little is known about surveillance patterns for surgically resected, early-stage lung cancer patients in the community-at-large. We sought to characterize surveillance patterns in a national cohort.
Methods
We conducted a retrospective study using Surveillance, Epidemiology, and End-Results (SEER)-Medicare database (1995-2010). Patients with stage I/II NSCLC treated with surgical resection were included. Our primary outcome was receipt of imaging between 4 and 8 months following surgery. Covariates included demographics and comorbidities.
Results
Chest radiography (CXR) was the most frequent initial modality (60%) followed by chest computerized tomography (CT) (25%). Positron emission tomography (PET) was least frequent as initial imaging modality (3%). A total of 13% of patients received no imaging within the initial surveillance period. Adherence to National Comprehensive Cancer Network (NCCN) guidelines for imaging by overall prevalence was 47% for receipt of CT, however rates of CT imaging increased over time from 28% to 61% (p<0.01). Reduced rates of CT imaging were associated with stage I disease and surgery as the sole treatment modality.
Conclusions
Imaging following definitive surgery for NSCLC predominantly utilizes CXR rather than CT. Most of this imaging is likely for surveillance and in that context, CXR has inferior detection rates for recurrence and detection of new cancers. Adherence to guideline recommended CT surveillance following surgery is poor, but the reason multifactorial. Efforts to improve adherence to imaging surveillance must be coupled with greater evidence demonstrating improved long-term outcomes.
doi:10.1016/j.athoracsur.2014.06.067
PMCID: PMC4256105  PMID: 25282167
5.  Multicenter Study Comparing Case Definitions Used to Identify Patients with Chronic Obstructive Pulmonary Disease 
Rationale: Clinical trials in chronic obstructive pulmonary disease (COPD) usually require evidence of airflow obstruction and clinical risk factors. International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes or patient-reported physician diagnoses are often used for epidemiologic studies and performance improvement programs.
Objectives: To evaluate agreement between these case definitions for COPD and to assess the comparability of study populations identified as having COPD not using the clinical trial reference standard.
Methods: We recruited patients from the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter clinical registry in a cross-sectional study. Demographics, clinical, and post-bronchodilator spirometry data were collected at an in-person study visit. The kappa statistic (κ) was used to evaluate agreement. A multivariable logistic regression model was used to identify patient characteristics associated with meeting the trial reference standard.
Measurements and Main Results: A total of 998 (82.8%) of 1,206 study participants met at least one case definition for COPD (of the 998: 91% using ICD-9 codes, 73% using patient-reported physician diagnosis, 56% using trial reference standard); agreement between case definitions was poor (κ = 0.20–0.26). Lack of airflow obstruction was the principal (89%) reason patients identified as having COPD did not meet the trial reference standard. Patients who were black (vs. white), obese (vs. normal weight), or had depression (vs. not) were less likely to meet the trial reference standard (odds ratio [95% CI], 0.37 [0.26–0.53], 0.51 [0.34–0.75], 0.53 [0.40–0.71], respectively).
Conclusions: Findings highlight concerns about the applicability of findings in clinical trials to patients meeting other case definitions for COPD.
doi:10.1164/rccm.201406-1166OC
PMCID: PMC4299587  PMID: 25192554
COPD; spirometry; ICD-9-CM; comparative effectiveness; case definitions
7.  Thiazolidinediones are associated with a reduced risk of COPD exacerbations 
Background
Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.
Objective
The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation.
Methods
A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007. Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication. Multivariable negative binomial regression was performed with adjustment for potential confounding factors. The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.
Results
We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications. COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group. In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81–0.92).
Conclusion
Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD.
doi:10.2147/COPD.S82643
PMCID: PMC4536761  PMID: 26300638
peroxisome proliferator-activated receptors; glitazones; COPD exacerbation; inflammation; cohort study
8.  Association between β-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension 
Thorax  2012;67(11):977-984.
Background
β-Blocker therapy has been shown to improve survival among patients with ischaemic heart disease (IHD) and congestive heart failure (CHF) and is underused among patients with chronic obstructive pulmonary disease (COPD). Evidence regarding the optimal use of β-blocker therapy during an acute exacerbation of COPD is particularly weak.
Methods
We conducted a retrospective cohort study of patients aged ≥40 years with IHD, CHF or hypertension who were hospitalised for an acute exacerbation of COPD from 1 January 2006 to 1 December 2007 at 404 acute care hospitals throughout the USA. We examined the association between β-blocker therapy and in-hospital mortality, initiation of mechanical ventilation after day 2 of hospitalisation, 30-day all-cause readmission and length of stay.
Results
Of 35 082 patients who met the inclusion criteria, 29% were treated with β blockers in the first two hospital days, including 22% with β1-selective and 7% with non-selective β blockers. In a propensity-matched analysis, there was no association between β-blocker therapy and in-hospital mortality (OR 0.88, 95% CI 0.71 to 1.09), 30-day readmission (OR 0.96, 95% CI 0.89 to 1.03) or late mechanical ventilation (OR 0.98, 95% CI 0.77 to 1.24). However, when compared with β1 selective β blockers, receipt of non-selective β blockers was associated with an increased risk of 30-day readmission (OR 1.25, 95% CI 1.08 to 1.44).
Conclusions
Among patients with IHD, CHF or hypertension, continuing β1-selective β blockers during hospitalisation for COPD appears to be safe. Until additional evidence becomes available, β1-selective β blockers may be superior to treatment with a non-selective β blocker.
doi:10.1136/thoraxjnl-2012-201945
PMCID: PMC4454610  PMID: 22941975
9.  The Epidemiology and Outcome of Prehospital Respiratory Distress 
Objectives
Patients with respiratory distress often seek emergency medical care, and are transported by emergency medical services (EMS). EMS encounters with patients in respiratory distress have not been well described. The study objective was to characterize the epidemiology of prehospital respiratory distress and subsequent patient outcomes.
Methods
This was a population-based cohort study of non-injured adults transported by EMS to any of 16 hospitals between 2002 and 2006. EMS records were linked to hospital administrative data for encounters categorized by EMS personnel as primarily “respiratory distress” in nature. The authors described prehospital patient and encounter characteristics, interventions, hospital discharge diagnoses (using ICD-9-CM codes), and patient outcomes. The association between prehospital variables, defined a priori, and hospital admission were described using multivariable logistic regression.
Results
There were 19,858 EMS encounters, of which 166,908 were for respiratory distress (11.9%, 95% confidence interval [CI] = 11.7% to 12.1%). Half of the patients were admitted to the hospital (n = 9,964), one-third of those required intensive care (n = 3,094), and 10% of hospitalized patients died prior to discharge (n = 948). Fifteen percent of hospitalized patients received invasive mechanical ventilation (n = 1,501), over half of whom were intubated during prehospital care (n = 896). The most common primary discharge diagnoses among prehospital respiratory distress patients admitted to the hospital were congestive heart failure (16%), pneumonia (15%), chronic obstructive pulmonary disease (13%), and acute respiratory failure (13%). Few EMS patients with respiratory distress were coded with a primary diagnosis of acute myocardial infarction (3.5%, n = 350), or underwent percutaneous coronary intervention (0.7%, n = 71). In a multivariable regression model, prehospital factors that were independently associated with hospital admission included initial respiratory rate (odds ratio [OR] 1.29 for an increase in respiratory rate of five breaths per minute, 95% CI = 1.24 to 1.35), and an encounter that originated at a nursing home (OR 2.80, 95% CI = 2.28 to 3.43).
Conclusions
In a ppulation-based cohort, EMS personnel commonly encounter prehospital respiratory distress among medical patients, many of whom require hospital admission to the intensive care unit. These data may help to inform targeted therapy or more efficient triage and transport decisions.
doi:10.1111/acem.12380
PMCID: PMC4247789  PMID: 24842506
10.  Association of Chronic Cough and Pulmonary Function with 6-Minute Walk Test Performance in HIV Infection 
Objective
Chronic lung disease has been associated with greater impairment in self-reported physical function in HIV patients. We sought to study this association using objective measures of physical or pulmonary function.
Design
Baseline data from the Examinations of HIV Associated Lung Emphysema (EXHALE) study, a multicenter observational cohort of HIV-infected and uninfected Veterans.
Methods
We assessed the association between clinical, laboratory, and pulmonary function measures on six-minute walk test (6-MWT). Multivariable linear regression models were generated to identify factors associated with 6-MWT performance.
Results
340 participants completed 6-MWT (mean age 55 years), with 68% black race, 94% men and 62% current smokers. Overall, 180 (53%) were HIV-infected and 63 (19%) had spirometry-defined COPD. In a multivariable model, age, current smoking, and obesity (BMI>30) were independently associated with lower 6-MWT performance, but HIV infection was not; there was a significant interaction between HIV and chronic cough, such that distance walked among HIV-infected participants with chronic cough was 51.76 meters less (p=0.04) compared to those without cough or HIV. Among HIV-infected participants, the forced expiratory volume in one second (FEV1, % predicted), to a greater extent than total lung capacity or diffusion capacity, attenuated the association with chronic cough; decreased FEV1 was independently associated with lower 6-MWT performance in those with HIV.
Conclusion
Older age, current smoking and airflow limitation were important determinants of 6-MWT performance in the HIV-infected participants. These findings suggest potential interventions to improve physical function may include early management of respiratory symptoms and airflow limitation.
doi:10.1097/QAI.0000000000000086
PMCID: PMC4405108  PMID: 24346638
Respiratory measurement; Immunodeficiency; Clinical epidemiology; 6-MWT; airflow limitation
11.  Penalizing Hospitals for Chronic Obstructive Pulmonary Disease Readmissions 
In October 2014, the U.S. Centers for Medicare and Medicaid Services (CMS) will expand its Hospital Readmission Reduction Program (HRRP) to include chronic obstructive pulmonary disease (COPD). Under the new policy, hospitals with high risk-adjusted, 30-day all-cause unplanned readmission rates after an index hospitalization for a COPD exacerbation will be penalized with reduced reimbursement for the treatment of Medicare beneficiaries. In this perspective, we review the history of the HRRP, including the recent addition of COPD to the policy. We critically assess the use of 30-day all-cause COPD readmissions as an accountability measure, discussing potential benefits and then highlighting the substantial drawbacks and potential unintended consequences of the measure that could adversely affect providers, hospitals, and patients with COPD. We conclude by emphasizing the need to place the 30-day COPD readmission measure in the context of a reconceived model for postdischarge quality and review several frameworks that could help guide this process.
doi:10.1164/rccm.201308-1541PP
PMCID: PMC3983837  PMID: 24460431
quality indicators; chronic obstructive pulmonary disease; patient readmission; Medicare
12.  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 (β = −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.
doi:10.1164/rccm.201212-2154OC
PMCID: PMC3827700  PMID: 23848267
pneumonia; dementia; cognitive function
13.  What the Heck is a “Nodule”? A Qualitative Study of Veterans with Pulmonary Nodules 
Rationale
Every year, hundreds of thousands of patients are diagnosed with incidentally-detected pulmonary nodules and if lung cancer screening is widely implemented, thousands more will be identified. The psychosocial outcomes associated with incidental nodule detection in general practice settings are virtually unknown.
Objective
The purpose of this study was to explore the experiences of patients with incidentally diagnosed pulmonary nodules.
Methods& Measurements
We conducted qualitative interviews of 19 Veterans with incidentally-detected pulmonary nodules. We used qualitative description for the analysis, focusing on patients’ information exchange and other communication behaviors with their clinicians.
Main Results
The patients were cared for by primary care clinicians and had small nodules that were unlikely to be malignant. Patients did not understand the term “nodule” although they knew it was related to cancer. They also did not understand the followup plan and most were unable to obtain better information from their clinician or other sources. Most patients experienced distress because of the nodule that was usually mild although sometimes severe. This distress was sometimes mitigated by patients’ confidence in their clinician. Most patients wanted more and better information about their nodule.
Conclusions
Veterans from one hospital have little understanding of what nodules are, the likelihood of malignancy, and the follow-up plan. Their reaction to this knowledge deficit is variable and is likely related to preferred communication behaviors with their clinician. Evaluating communication in other settings is important to confirm these findings and refine mechanisms to improve patient-centered care for those with incidentally-detected pulmonary nodules.
doi:10.1513/AnnalsATS.201304-080OC
PMCID: PMC3780978  PMID: 23952851
pulmonary nodule; lung cancer; patient-centered outcomes; communication
14.  Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study 
Background
Thiazolidinediones are oral diabetes medications that selectively activate peroxisome proliferator-activated receptor gamma and have potent anti-inflammatory properties. While a few studies have found improvements in pulmonary function with exposure to thiazolidinediones, there are no studies of their impact on asthma exacerbations. Our objective was to assess whether exposure to thiazolidinediones was associated with a decreased risk of asthma exacerbation.
Methods
We performed a cohort study of diabetic Veterans who had a diagnosis of asthma and were taking oral diabetes medications during the period of 10/1/2005 – 9/30/2006. The risk of asthma exacerbations and oral steroid use during 10/1/2006 – 9/30/2007 was compared between patients who were prescribed thiazolidinediones and patients who were on alternative oral diabetes medications. Multivariable logistic regression and negative binomial regression analyses were used to characterize this risk. A sensitivity analysis was performed, restricting our evaluation to patients who were adherent to diabetes therapy.
Results
We identified 2,178 patients who were on thiazolidinediones and 10,700 who were not. Exposure to thiazolidinediones was associated with significant reductions in the risk of asthma exacerbation (OR = 0.79, 95% CI, 0.62 – 0.99) and oral steroid prescription (OR = 0.73, 95% CI 0.63 – 0.84). Among patients who were adherent to diabetes medications, there were more substantial reductions in the risks for asthma exacerbation (OR = 0.64, 95% CI 0.47 – 0.85) and oral steroid prescription (OR = 0.68, 95% CI 0.57 – 0.81).
Conclusions
Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids.
doi:10.1186/1710-1492-10-34
PMCID: PMC4094895  PMID: 25024717
Thiazolidinediones; Peroxisome proliferator-activated receptors; Glitazones; Asthma; Cohort study
15.  Life-Sustaining-Treatment Preferences: Matches and Mismatches Between Patients’ Preferences and Clinicians’ Perceptions 
Context
Better clinician understanding of patients’ end-of-life-treatment preferences has the potential for reducing unwanted treatment, decreasing health care costs, and improving end-of-life care.
Objectives
To investigate patient preferences for life-sustaining therapies, clinicians’ accuracy in understanding those preferences, and predictors of patient preference and clinician error.
Methods
Observational study of 196 male veterans with chronic obstructive pulmonary disease (COPD) who participated in a randomized trial. Measures included patients’ preferences for mechanical ventilation (MV) and cardiopulmonary resuscitation (CPR) if needed in their current state of health, and outpatient clinicians’ beliefs about those preferences.
Results
Analyses were based on 54% of participants in the trial who had complete patient/clinician data on treatment preferences. Patients were more receptive to CPR than MV (76% vs. 61%; P<0.001). Preferences for both treatments were significantly associated with the importance patients assigned to avoiding life-sustaining therapies during the final week of life (MV: b=−0.11, P<0.001; CPR: b=−0.09, P=0.001). When responses were dichotomized (would/wouldn’t want treatment), physicians’ perceptions matched patient preferences in 75% of CPR cases and 61% of MV cases. Physician errors increased as patients preferred less aggressive treatment (MV: b=−0.28, P<0.001; CPR: b=−0.32, P<0.001).
Conclusion
Clinicians erred more often about patients’ wishes when patients did not want treatment than when they wanted it. Treatment decisions based on clinicians’ perceptions could result in costly and unwanted treatments. End-of-life care could benefit from increased clinician-patient discussion about end-of-life care, particularly if discussions included patient education about risks of treatment and allowed clinicians to form and maintain accurate impressions of patients’ preferences.
doi:10.1016/j.jpainsymman.2012.07.002
PMCID: PMC3534846  PMID: 23017611
treatment preferences; patient-clinician communication; chronic obstructive pulmonary disease; palliative care
16.  Coexisting chronic conditions associated with mortality and morbidity in adult patients with asthma 
Objective
Many asthma patients suffer from chronic conditions other than asthma. We investigated the specific contribution of common comorbidities on mortality and morbidity in adult asthma.
Methods
In an observational study of adults with incident asthma identified between 1999 and 2003 using National Veterans Affairs and Centers for Medicare and Medicaid Services encounter databases (n=25,975, follow-up 3.0±1.7 years), association between 13 most prevalent comorbidities (hypertension, ischemic heart disease (IHD), osteoarthritis, rheumatoid arthritis, diabetes, mental disorders, substance/drug abuse, enlarged prostate, depression, cancer, alcoholism, HIV, and heart failure) and 4 conditions previously associated with asthma (sleep apnea, gastroesophageal reflux disease (GERD), rhinitis, and sinusitis) and mortality, hospitalizations and asthma exacerbations were assessed using multivariate regression analyses adjusted for other clinically important covariates.
Results
HIV followed by alcoholism and mental disorders among 18–45 years old, and heart failure, diabetes, IHD, and cancer among those ≥65 years old were associated with an increased risk of all-cause mortality. Many conditions were associated with increased risk for all-cause hospitalizations, but the increased risk was consistent across all ages for mental disorders. For asthma exacerbations, mental disorder followed by substance abuse and IHD were associated with increased risk among those 18–45 years old, and chronic sinusitis, mental disorder, and IHD among those ≥65 years old. GERD was associated with decreased risk for asthma exacerbation in all ages.
Conclusions
Many comorbidities are associated with poor outcome in adult asthmatics and their effect differs by age. Mental disorders are associated with increased risk of mortality and morbidity across ages.
doi:10.3109/02770903.2013.879881
PMCID: PMC4067514  PMID: 24432868
observational study; Veterans; outcome research; comorbidities; mental disorders
17.  Measuring health-related quality of life in chronic obstructive pulmonary disease: properties of the EQ-5D-5L and PROMIS-43 short form 
Background
The Patient Reported Outcomes Measurement Information System 43-item short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed measures of health-related quality of life (HRQL) that have potentially broad application in evaluating treatments and capturing burden of respiratory-related diseases. The aims of this study were: (1) to examine their psychometric properties in patients with chronic obstructive pulmonary disease (COPD), and (2) to identify dimensions of HRQL that differ and do not differ by lung function.
Methods
We conducted a multi-center, cross-sectional study (“COPD Outcomes-based Network for Clinical Effectiveness & Research Translation” [CONCERT]). We analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L and PROMIS questionnaires. Disease severity was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Pulmonary function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ-VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT-Dyspnea) were administered. Validity and reliability of EQ-5D-5L and PROMIS-43 were examined, and differences in HRQL by GOLD grade were assessed.
Results
Data from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male). More severe COPD was associated with more problems with mobility, self-care and usual activities (all p-values <0.01) according to EQ-5D-5L. Related domains on EQ-5D-5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) correlated. A statistically significant trend of decreasing HRQL with more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores, and PROMIS physical function and social roles.
Conclusions
Results supported the validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical function and social activities decrease with level of lung function by GOLD grade, but not pain, mental health, sleep or fatigue as reported by patients.
doi:10.1186/1471-2288-14-78
PMCID: PMC4072614  PMID: 24934150
COPD; EQ-5D-5L; PROMIS; Psychometric properties
18.  Predictors of Adherence to Inhaled Medications 
doi:10.1007/s11606-013-2383-7
PMCID: PMC3663956  PMID: 23529709
20.  Wide Clinic-Level Variation in Adherence to Oral Diabetes Medications in the VA 
ABSTRACT
BACKGROUND
While there has been extensive research into patient-specific predictors of medication adherence and patient-specific interventions to improve adherence, there has been little examination of variation in clinic-level medication adherence.
OBJECTIVE
We examined the clinic-level variation of oral hypoglycemic agent (OHA) medication adherence among patients with diabetes treated in the Department of Veterans Affairs (VA) primary care clinics. We hypothesized that there would be systematic variation in clinic-level adherence measures, and that adherence within organizationally-affiliated clinics, such as those sharing local management and support, would be more highly correlated than adherence between unaffiliated clinics.
DESIGN
Retrospective cohort study.
SETTING
VA hospital and VA community-based primary care clinics in the contiguous 48 states.
PATIENTS
444,418 patients with diabetes treated with OHAs and seen in 158 hospital-based clinics and 401 affiliated community primary care clinics during fiscal years 2006 and 2007.
MAIN MEASURES
Refill-based medication adherence to OHA.
KEY RESULTS
Adjusting for patient characteristics, the proportion of patients adherent to OHAs ranged from 57 % to 81 % across clinics. Adherence between organizationally affiliated clinics was high (Pearson Correlation = 0.82), and adherence between unaffiliated clinics was low (Pearson Correlation = 0.04).
CONCLUSION
The proportion of patients adherent to OHAs varied widely across VA primary care clinics. Clinic-level adherence was highly correlated to other clinics in the same organizational unit. Further research should identify which factors common to affiliated clinics influence medication adherence.
doi:10.1007/s11606-012-2331-y
PMCID: PMC3631064  PMID: 23371383
pharmacoepidemiology; health services research; diabetes; veterans; primary care
21.  Missing Potential Opportunities to Reduce Repeat COPD Exacerbations 
Introduction
Long-acting beta-agonists (LABA) and/or inhaled corticosteroids (ICS) have been shown to reduce COPD exacerbation risk. Using data from a large integrated health-care system, we sought to examine whether these medication classes were initiated after an exacerbation of COPD.
Methods
We identified patients who experienced an inpatient or outpatient COPD exacerbation within the Veterans Affairs Integrated Service Network (VISN)-20. We assessed the addition of a new inhaled therapy (an ICS, LABA or both) within 180 days after the exacerbation. We assessed independent predictors of adding treatment using logistic regression.
Results
We identified 45,780 patients with COPD, of whom 2,760 patients experienced an exacerbation of COPD. Of these individuals, 2,570 (93.1 %) were on either none or only one long-acting medication studied (LABA or ICS). In the subsequent 180-day period after their exacerbation, only 875 (34.1 %) patients had at least one of these additional therapies dispensed from a VA pharmacy. Among patients who were treated in the outpatient setting, older age [OR 0.98/year, 95 % CI (0.97–0.99)], current tobacco use [OR 0.74, 95 % CI (0.60–0.90)], greater use of ipratropium bromide [OR 0.97/canister, 95 % CI (0.96–0.98)], prior COPD exacerbation [OR 0.55, 95 % CI (0.46–0.67)], depression [OR 0.77, 95 % CI (0.61–0.98)], CHF [OR 0.74, 95 % CI (0.57–0.97)], and diabetes (OR 0.77 (0.60–0.99)] were associated with lower odds of additional therapy. Patients who were treated in the hospital had similar associated predictors.
Conclusion
Among patients treated for an exacerbation of COPD, we found relatively few were subsequently prescribed inhaled therapies known to reduce exacerbations.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2276-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-012-2276-1
PMCID: PMC3631056  PMID: 23225255
COPD; exacerbation; inhaled medication use
22.  Obesity Is Associated With a Lower Resting Oxygen Saturation in the Ambulatory Elderly: Results From the Cardiovascular Health Study 
Respiratory care  2013;58(5):10.4187/respcare.02008.
BACKGROUND
The contribution of obesity to hypoxemia has not been reported in a community-based study. Our hypothesis was that increasing obesity would be independently associated with lower SpO2 in an ambulatory elderly population.
METHODS
The Cardiovascular Health Study ascertained resting SpO2 in 2,252 subjects over age 64. We used multiple linear regression to estimate the association of body mass index (BMI) with SpO2 and to adjust for potentially confounding factors. Covariates including age, sex, race, smoking, airway obstruction (based on spirometry), self reported diagnosis of emphysema, asthma, heart failure, and left ventricular function (by echocardiography) were evaluated.
RESULTS
Among 2,252 subjects the mean and median SpO2 were 97.6% and 98.0% respectively; 5% of subjects had SpO2 values below 95%. BMI was negatively correlated with SpO2 (Spearman R = −0.27, P < .001). The mean difference in SpO2 between the lowest and highest BMI categories (< 25 kg/m2 and ≥ 35 kg/m2) was 1.33% (95% CI 0.89–1.78%). In multivariable linear regression analysis, SpO2 was significantly inversely associated with BMI (1.4% per 10 units of BMI, 95% CI 1.2–1.6, for whites/others, and 0.87% per 10 units of BMI, 95% CI 0.47–1.27, for African Americans).
CONCLUSIONS
We found a narrow distribution of SpO2 values in a community-based sample of ambulatory elderly. Obesity was a strong independent contributor to a low SpO2, with effects comparable to or greater than other factors clinically associated with lower SpO2.
doi:10.4187/respcare.02008
PMCID: PMC3885157  PMID: 23107018
pulse oximetry; oxygen; obesity; body mass index; waist circumference; hypoxemia; pulmonary function test
23.  Use of Spirometry in the Diagnosis of COPD: A Qualitative Study in Primary Care 
COPD  2013;10(4):444-449.
Guidelines that recommend spirometry to confirm airflow obstruction among patients with suspected COPD are not routinely followed. We conducted a qualitative study to identify attitudes and barriers of primary care physicians to performing spirometry for patients with possible COPD. We conducted four focus groups, each with three primary care physicians (PCPs) who practice in an urban, academic medical center. In general, PCPs believed that spirometry was not necessary to confirm the diagnosis of COPD. Compared to other co-morbid conditions, in a patient with a diagnosis of COPD without self-reported symptoms, COPD was not a priority during a clinic visit. This was in part due to the belief that there was lack of evidence that medication used in COPD lead to improved outcomes and that there was no point of care measure for COPD compared to other co-morbid conditions such as diabetes mellitus or hypertension. Health system barriers specific to spirometry use was not identified. In conclusion, in our sample of PCPs, there was skepticism that spirometry is warranted to diagnose and manage COPD. Availability of spirometry was not a perceived barrier. Our results explain, in part, why previous interventions to improve access to spirometry and diagnosis of COPD in primary care settings have been difficult to conduct and/or have had marginal success. Our findings strongly suggest that a first step toward increasing the use of spirometry among primary care physicians is to have them believe in its utility in the diagnosis of COPD.
doi:10.3109/15412555.2013.766683
PMCID: PMC3938329  PMID: 23537230
chronic disease; diagnosis; pulmonary diseases; qualitative research
24.  Stakeholder Priorities for Comparative Effectiveness Research in Chronic Obstructive Pulmonary Disease 
Comparative effectiveness research (CER) is intended to address the expressed needs of patients, clinicians, and other stakeholders. Representatives of 54 stakeholder groups with an interest in chronic obstructive pulmonary disease (COPD) participated in workshops convened by the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period. Year 1 focused on chronic care and care coordination. Year 2 focused on acute care and transitions in care between healthcare settings. Discussions and provisional voting were conducted via teleconferences and e-mail exchanges before the workshop. Final prioritization votes occurred after in-person discussions at the workshop. We used a modified Delphi approach to facilitate discussions and consensus building. To more easily quantify preferences and to evaluate the internal consistency of rankings, the Analytic Hierarchy Process was incorporated in Year 2. Results of preworkshop and final workshop voting often differed, suggesting that prioritization efforts relying solely on requests for topics from stakeholder groups without in-person discussion may provide different research priorities. Research priorities varied across stakeholder groups, but generally focused on studies to evaluate different approaches to healthcare delivery (e.g., spirometry for diagnosis and treatment, integrated healthcare strategies during transitions in care) rather than head-to-head comparisons of medications. This research agenda may help to inform groups intending to respond to CER funding opportunities in COPD. The methodologies used, detailed in the online supplement, may also help to inform prioritization efforts for CER in other health conditions.
doi:10.1164/rccm.201206-0994WS
PMCID: PMC3603554  PMID: 23155144
health services research; research priorities; care coordination; stakeholders
25.  Predictors of Adherence to Inhaled Medications Among Veterans with COPD 
Journal of General Internal Medicine  2012;27(11):1506-1512.
ABSTRACT
BACKGROUND
Factors contributing to medication nonadherence among patients with chronic obstructive pulmonary disease (COPD) are poorly understood.
OBJECTIVES
To identify patient characteristics that are predictive of adherence to inhaled medications for COPD and, for patients on multiple inhalers, to assess whether adherence to one medication class was associated with adherence to other medication classes.
DESIGN
Cohort study using data from Veteran Affairs (VA) electronic databases.
PARTICIPANTS
This study included 2,730 patients who underwent pulmonary function testing between 2003 and 2007 at VA facilities in the Northwestern United States, and who met criteria for COPD.
MAIN MEASURES
We used pharmacy records to estimate adherence to inhaled corticosteroids (ICS), ipratropium bromide (IP), and long-acting beta-agonists (LABA) over two consecutive six month periods. We defined patients as adherent if they had refilled medications to have 80 % of drug available over the time period. We also collected information on their demographics, behavioral habits, COPD severity, and comorbidities.
KEY RESULTS
Adherence to medications was poor, with 19.8 % adherent to ICS, 30.6 % adherent to LABA, and 25.6 % adherent to IP. Predictors of adherence to inhaled therapies were highly variable and dependent on the medication being examined. In adjusted analysis, being adherent to a medication at baseline was the strongest predictor of future adherence to that same medication [(Odds ratio, 95 % confidence interval) ICS: 4.79 (3.22–7.12); LABA: 6.60 (3.92–11.11); IP: 14.13 (10.00–19.97)], but did not reliably predict adherence to other classes of medication.
CONCLUSIONS
Among patients with COPD, past adherence to one class of inhaled medication strongly predicted future adherence to the same class of medication, but only weakly predicted adherence to other classes of medication.
doi:10.1007/s11606-012-2130-5
PMCID: PMC3475808  PMID: 22782274
medication adherence; pulmonary diseases; health behavior; veterans

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