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1.  Predicting Antibiotic Resistance to Community-Acquired Pneumonia Antibiotics in Culture-Positive Patients With Healthcare-Associated Pneumonia 
Journal of hospital medicine  2011;7(3):195-202.
To develop and validate a model to predict resistance to community-acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare-associated pneumonia (HCAP), and to compare the model’s predictive performance to a model including only guideline-defined criteria for HCAP.
Retrospective cohort study.
Six Veterans Affairs Medical Centers in the northwestern United States.
Culture-positive inpatients with HCAP.
Patients were identified based upon guideline-defined criteria for HCAP. Relevant cultures obtained within 48 hours of admission were assessed to determine bacteriology and antibiotic susceptibility. Medical records for the year preceding admission were assessed to develop predictive models of CAP-resistance with logistic regression. The predictive performance of cohort-developed and guideline-defined models was compared.
CAP-resistant organisms were identified in 118 of 375 culture-positive patients. Of guideline-defined criteria, CAP-resistance was associated (odds ratio (OR) [95% confidence interval (CI)]) with: admission from nursing home (2.6 [1.6–4.4]); recent antibiotic exposure (1.7 [1.0–2.8]); and prior hospitalization (1.6 [1.0–2.6]). In the cohort-developed model, CAP-resistance was associated with: admission from nursing home or recent nursing home discharge (2.3 [1.4–3.8]); positive methicillin-resistant Staphylococcus aureus (MRSA) history within 90 days of admission (6.4 [2.6–17.8]) or 91–365 days (2.3 [0.9–5.9]); cephalosporin exposure (1.8 [1.1–2.9]); recent infusion therapy (1.9 [1.0–3.5]); diabetes (1.7 [1.0–2.8]); and intensive care unit (ICU) admission (1.6 [1.0–2.6]). Area under the receiver operating characteristic curve (aROC [95% CI]) for the cohort-developed model (0.71 [0.65–0.77]) was significantly higher than for the guideline-defined model (0.63 [0.57–0.69]) (P = 0.01).
Select guideline-defined criteria predicted CAP-resistance. A cohort-developed model based primarily on prior MRSA history, nursing home residence, and specific antibiotic exposures provided improved prediction of CAP-resistant organisms in HCAP.
PMCID: PMC4778425  PMID: 22038859
2.  COPD disease severity and innate immune response to pathogen-associated molecular patterns 
The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student’s t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%–80%) and 16 severe COPD (FEV1 <50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1β. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response.
PMCID: PMC4786062  PMID: 27019597
chronic obstructive pulmonary disease; innate immunity; inflammation; chronic bronchitis; toll-like receptors
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.
PMCID: PMC4342801  PMID: 25493656
quality of life; critical illness; intensive care units; cohort studies; outcome assessment (health care)
4.  Disability and Recovery of Independent Function in Obstructive Lung Disease: The Cardiovascular Health Study 
Chronic obstructive lung disease frequently leads to disability. Older patients may transition between disability and independence over time.
To identify factors associated with transitions between disability and independent function in obstructive lung disease.
We analyzed data for 4,394 participants in the Cardiovascular Health Study who completed pre-bronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 Instrumental Activity of Daily Living (IADL) or ≥1 Activity of Daily Living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk regression.
The prevalence of IADL impairment was higher among moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p<0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In adjusted analyses, airflow obstruction predicted development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment (RR 0.67, 95% CI 0.49-0.94). Compared to the most active persons (≥28 blocks walked per week), walking less was associated with decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81, 0.69-0.86, and < 7 blocks: RR 0.73, 0.61 -0.86). Increased strength (RR 1.16, 1.05-1.29) was associated with resolving IADL impairment.
Disability is common in older persons, especially those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research on interventions to improve these factors among patients with obstructive lung disease and disability is needed.
PMCID: PMC4197928  PMID: 25228204
chronic airflow obstruction; activities of daily living; disability
5.  Dyspnea and Pain Frequently Co-occur among Medicare Managed Care Recipients 
Rationale: Experimental and neuroimaging studies have suggested strong associations between dyspnea and pain. The co-occurrence of these symptoms has not been examined in community samples.
Objectives: We sought to ascertain the co-occurrence of pain and dyspnea by self-report in a large cohort of Medicare recipients.
Methods: We analyzed data from 266,000 Medicare Managed Care recipients surveyed in 2010 and 2012. Dyspnea was defined by aggregating three questions about shortness of breath (at rest, while walking one block, and while climbing stairs). Pain was measured by four questions about pain interference, chest pain, back pain, and arthritis pain. All measures were dichotomized as high or low/none. We calculated the co-occurrence of pain and dyspnea at baseline, and generated logistic regression models to find the adjusted relative risk (RR) of their co-occurrence, adjusting for patient-level factors and three potential medical causes of dyspnea (chronic obstructive pulmonary disease/emphysema/asthma, congestive heart failure, and obesity). We modeled the simultaneous development and the simultaneous resolution of dyspnea and pain between baseline and 2 years.
Measurements and Main Results: Participants with dyspnea had considerably higher prevalence of pain than those without (64 vs. 18%). In fully adjusted models, participants with any of the types of pain were substantially more likely to report dyspnea than those without these types of pain (high pain interference: relative risk [RR], 1.99; 95% confidence interval [CI], 1.92–2.07; chest pain: RR, 2.11; 95% CI, 2.04–2.18; back pain: RR, 1.76; 95% CI, 1.71–1.82; and arthritis pain: RR, 1.49; 95% CI, 1.44–1.54). The relative risks of dyspnea developing or resolving at 2 years were greatly increased (RRs of 1.5 – 4) if pain also developed or resolved.
Conclusions: Pain and dyspnea commonly occurred, developed, and resolved together. Most older adults with dyspnea also reported pain. Medical conditions typically assumed to cause dyspnea did not account for this association. The most plausible explanation for the co-occurrence is physical deconditioning.
PMCID: PMC4213996  PMID: 24960243
dyspnea; pain; shortness of breath; Medicare
6.  Improved Analgesia, Sedation, and Delirium Protocol Associated with Decreased Duration of Delirium and Mechanical Ventilation 
Rationale: Introduction of sedation protocols has been associated with improved patient outcomes. It is not known if an update to an existing high-quality sedation protocol, featuring increased patient assessment and reduced benzodiazepine exposure, is associated with improved patient process and outcome quality metrics.
Methods: This was an observational before (n = 703) and after (n = 780) cohort study of mechanically ventilated patients in a 24-bed trauma-surgical intensive care unit (ICU) from 2009 to 2011. The three main protocol updates were: (1) requirement to document Richmond Agitation Sedation Scale (RASS) scores every 4 hours, (2) requirement to document Confusion Assessment Method-ICU (CAM ICU) twice daily, and (3) systematic, protocolized deescalation of excess sedation. Multivariable linear regression was used for the primary analysis. The primary outcome was the duration of mechanical ventilation. Prespecified secondary endpoints included days of delirium; the frequency of patient assessment with the RASS and CAM-ICU instruments; benzodiazepine dosing; durations of mechanical ventilation, ICU stay, and hospitalization; and hospital mortality and ventilator associated pneumonia rate.
Results: Patients in the updated protocol cohort had 1.22 more RASS assessments per day (5.38 vs. 4.16; 95% confidence interval [CI], 1.05–1.39; P < 0.01) and 1.15 more CAM-ICU assessments per day (1.49 vs. 0.35; 95% CI, 1.08–1.21; P < 0.01) than the baseline cohort. The mean hourly benzodiazepine dose decreased by 34.8% (0.08 mg lorazepam equivalents/h; 0.15 vs. 0.23; P < 0.01). In the multivariable model, the median duration of mechanical ventilation decreased by 17.6% (95% CI, 0.6–31.7%; P = 0.04). The overall odds ratio of delirium was 0.67 (95% CI, 0.49–0.91; P = 0.01) comparing updated versus baseline cohort. A 12.4% reduction in median duration of ICU stay (95% CI, 0.5–22.8%; P = 0.04) and a 14.0% reduction in median duration of hospitalization (95% CI, 2.0–24.5%; P = 0.02) were also seen. No significant association with mortality (odds ratio, 1.18; 95% CI, 0.80–1.76; P = 0.40) was seen.
Conclusions: Implementation of an updated ICU analgesia, sedation, and delirium protocol was associated with an increase in RASS and CAM-ICU assessment and documentation; reduced hourly benzodiazepine dose; and decreased delirium and median durations of mechanical ventilation, ICU stay, and hospitalization.
PMCID: PMC4028734  PMID: 24597599
critical care; protocol; delirium; quality improvement
7.  Prevalence and correlates of suicide ideation in patients with COPD: a mixed methods study 
The purpose of this study was to examine the prevalence and correlates of suicidal ideation (SI) in patients with stable moderate to very severe chronic obstructive pulmonary disease (COPD).
Patients and methods
We conducted an exploratory mixed methods analysis of data from participants in a longitudinal observational study of depression in COPD. We measured depression with the Patient Health Questionnaire-9 (PHQ-9), which includes an item on SI. We compared participants with and without SI in relation to sociodemographics, symptoms, anxiety, and healthcare resource use with independent t-tests and chi-square tests. Content analysis was performed on qualitative data gathered during a structured SI safety assessment.
Of 202 participants, 121 (60%) had depressive symptoms (PHQ ≥6); 51 (25%) had a PHQ-9 ≥10, indicating a high likelihood of current major depression; and 22 (11%) reported SI. Compared to the 99 depressed participants without SI, those with SI were more likely to be female (59% vs 27%, P=0.004); had worse dyspnea (P=0.009), depression (P<0.001), and anxiety (P=0.003); and were also more likely to have received treatment for depression and/or anxiety (82% vs 40%, P<0.001) and more hospitalizations for COPD exacerbations (P=0.03) but had similar levels of airflow obstruction and functioning than participants without SI. Themes from the qualitative analysis among those with SI included current or prior adverse life situations, untreated or partially treated complex depression, loss of a key relationship, experience of illness and disability, and poor communication with providers.
Our findings suggest that current SI is common in COPD, may occur disproportionately in women, can persist despite mental health treatment, and has complex relationships with both health and life events. Adequate management of SI in COPD may therefore require tailored, comprehensive treatment approaches that integrate medical and mental health objectives.
PMCID: PMC4262376  PMID: 25587219
depression; qualitative; PHQ-9; suicide; pulmonary disease; chronic obstructive
8.  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.
PMCID: PMC3827700  PMID: 23848267
pneumonia; dementia; cognitive function
9.  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.
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.
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.
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).
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.
PMCID: PMC3885157  PMID: 23107018
pulse oximetry; oxygen; obesity; body mass index; waist circumference; hypoxemia; pulmonary function test
10.  Effects of respiratory and non-respiratory factors on disability among older adults with airway obstruction: The Cardiovascular Health Study 
COPD  2013;10(5):588-596.
High rates of disability associated with chronic airway obstruction may be caused by impaired pulmonary function, pulmonary symptoms, other chronic diseases, or systemic inflammation.
We analyzed data from the Cardiovascular Health Study, a longitudinal cohort of 5888 older adults. Categories of lung function (normal; restricted; borderline, mild-moderate, and severe obstruction) were delineated by baseline spirometry (without bronchodilator). Disability-free years were calculated as total years alive and without self-report of difficulty performing ≥1 Instrumental Activities of Daily Living over 6 years of follow-up. Using linear regression, we compared disability-free years by lung disease category, adjusting for demographic factors, body mass index, smoking, cognition, and other chronic comorbidities. Among participants with airflow obstruction, we examined the association of respiratory factors (FEV1 and dyspnea) and non-respiratory factors (ischemic heart disease, congestive heart failure, diabetes, muscle weakness, osteoporosis, depression and cognitive impairment) on disability-free years.
The average disability free years were 4.0 out of a possible 6 years. Severe obstruction was associated with 1 fewer disability-free year compared to normal spirometry in the adjusted model. For the 1,048 participants with airway obstruction, both respiratory factors (FEV1 and dyspnea) and non-respiratory factors (heart disease, coronary artery disease, diabetes, depression, osteoporosis, cognitive function, and weakness) were associated with decreased disability-free years.
Severe obstruction is associated with greater disability compared to patients with normal spirometery. Both respiratory and non-respiratory factors contribute to disability in older adults with abnormal spirometry.
PMCID: PMC3903127  PMID: 23819728
Chronic airflow obstruction; instrumental activities of daily living; disability; disablement process
11.  Navigational Bronchoscopy with Biopsy versus CT-guided Biopsy for the Diagnosis of a Solitary Pulmonary Nodule: A Cost-Consequences Analysis 
Solitary pulmonary nodules (SPN) are frequent and can be malignant. Both CT-guided biopsy and electromagnetic navigational bronchoscopy (ENB) with biopsy can be used to diagnose a SPN. A non-diagnostic CT-guided or ENB biopsy is often followed by VATS biopsy. The relative costs and consequences of these strategies are not known.
A decision tree was created with values from the literature to evaluate the clinical consequences and societal costs of a CT-guided biopsy strategy versus an ENB biopsy strategy for the diagnosis of a SPN. The serial use of ENB after non-diagnostic CT-guided biopsy and CT-guided biopsy after non-diagnostic ENB biopsy were tested as alternate strategies.
In a hypothetical cohort of 100 patients, use of the ENB biopsy strategy on average results in 13.4 fewer pneumothoraces, 5.9 fewer chest tubes, 0.9 fewer significant hemorrhage episodes and 0.6 fewer respiratory failure episodes than a CT-guided biopsy strategy. ENB biopsy increases average costs by $3719 per case and increases video assisted thorascopic surgery (VATS) rates by an absolute 20%. The sequential diagnostic strategy that combines CT-guided biopsy after non-diagnostic ENB biopsy and vice-versa decreases the rate of VATS procedures to 3%. A sequential approach starting with ENB decreases average per case cost relative to CT-guided biopsy followed by VATS, if needed, by $507; and a sequential approach starting with CT-guided biopsy decreases the cost relative to CT-guided biopsy followed by VATS, if needed, by $979.
An ENB with biopsy strategy is associated with decreased pneumothorax rate but increased costs and increased use of VATS. Combining CT-guided biopsy and ENB with biopsy serially can decrease costs and complications.
PMCID: PMC3611239  PMID: 23207529
12.  Guideline-Based Antibiotics and Mortality in Healthcare-Associated Pneumonia 
Guidelines recommend administration of antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear if this therapy improves outcomes for patients with HCAP.
To determine if administration of guideline-similar therapy (GST) was associated with a reduction in 30-day mortality for HCAP.
Multi-center retrospective study.
Thirteen hundred and eleven admissions for HCAP in six Veterans Affairs Medical Centers.
Each admission was classified as receiving GST, anti-MRSA or anti-pseudomonal components of GST, or other non-HCAP therapy initiated within 48 hours of hospitalization. Association between 30-day mortality and GST was estimated with a logistic regression model that included GST, propensity to receive GST, probability of recovering an organism from culture resistant to antibiotics traditionally used to treat community-acquired pneumonia (CAP-resistance), and a GST by CAP-resistance probability interaction.
Main Measures
Odds ratios and 95% confidence intervals [OR (95% CI)] of 30-day mortality for patients treated with GST and predicted probability of recovering a CAP-resistant organism, and ratio of odds ratios [ROR (95% CI)] for treatment by CAP-resistance probability interaction.
Key Results
Receipt of GST was associated with increased odds of 30-day mortality [OR = 2.11 (1.11, 4.04), P = 0.02)] as was the predicted probability of recovering a CAP-resistant organism [OR = 1.67 (1.26, 2.20), P < 0.001 for a 25% increase in probability]. An interaction between predicted probability of recovering a CAP-resistant organism and receipt of GST demonstrated lower mortality with GST at high probability of CAP resistance [ROR = 0.71(≤1.00) for a 25% increase in probability, P = 0.05].
For HCAP patients with high probability of CAP-resistant organisms, GST was associated with lower mortality. Consideration of the magnitude of patient-specific risk for CAP-resistant organisms should be considered when selecting HCAP therapy.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2011-y) contains supplementary material, which is available to authorized users.
PMCID: PMC3378737  PMID: 22396110
pneumonia; anti-bacterial agents; guideline; methicillin-resistant Staphylococcus aureus; Pseudomonas aeruginosa; healthcare-associated infection
13.  Association between hospital volume and network membership and an analgesia, sedation and delirium order set quality score: a cohort study 
Critical Care  2012;16(3):R106.
Protocols for the delivery of analgesia, sedation and delirium care of the critically ill, mechanically ventilated patient have been shown to improve outcomes but are not uniformly used. The extent to which elements of analgesia, sedation and delirium guidelines are incorporated into order sets at hospitals across a geographic area is not known. We hypothesized that both greater hospital volume and membership in a hospital network are associated with greater adherence of order sets to sedation guidelines.
Sedation order sets from all nonfederal hospitals without pediatric designation in Washington State that provided ongoing care to mechanically ventilated patients were collected and their content systematically abstracted. Hospital data were collected from Washington State sources and interviews with ICU leadership in each hospital. An expert-validated score of order set quality was created based on the 2002 four-society guidelines. Clustered multivariable linear regression was used to assess the relationship between hospital characteristics and the order set quality score.
Fifty-one Washington State hospitals met the inclusion criteria and all provided order sets. Based on expert consensus, 21 elements were included in the analgesia, sedation and delirium order set quality score. Each element was equally weighted and contributed one point to the score. Hospital order set quality scores ranged from 0 to 19 (median = 8, interquartile range 6 to 14). In multivariable analysis, a greater number of acute care days (P = 0.01) and membership in a larger hospital network (P = 0.01) were independently associated with a greater quality score.
Hospital volume and membership in a larger hospital network were independently associated with a higher quality score for ICU analgesia, sedation and delirium order sets. Further research is needed to determine whether greater order-set quality is associated with improved outcomes in the critically ill. The development of critical care networks might be one strategy to improve order set quality scores.
PMCID: PMC3580663  PMID: 22709540
14.  Anxiety is associated with diminished exercise performance and quality of life in severe emphysema: a cross-sectional study 
Respiratory Research  2010;11(1):29.
Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability. The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea.
Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St. Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI).
Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001). Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ.
In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes.
Trail Registration NCT00000606
PMCID: PMC2848143  PMID: 20214820
15.  Polymorphic Variation in Surfactant Protein B is Associated with COPD Exacerbations 
COPD exacerbations reduce quality of life and increase mortality. Genetic variation may explain the substantial variability seen in exacerbation frequency among COPD subjects with similar lung function. We analyzed whether polymorphisms in five candidate genes previously associated with COPD susceptibility also demonstrate association with COPD exacerbations.
Eighty-eight single nucleotide polymorphisms in microsomal epoxide hydrolase (EPHX1), transforming growth factor beta 1 (TGFB1), SERPINE2, glutathione S-transferase pi (GSTP1), and surfactant protein B (SFTPB) were genotyped in 389 non-Hispanic white participants in the National Emphysema Treatment Trial. Exacerbations were defined as COPD-related emergency room visits or hospitalizations using Centers for Medicare and Medicaid Services claims data.
Measurements and Main Results
216 subjects (56%) experienced one or more exacerbations during the study period. An SFTPB promoter polymorphism, rs3024791, was associated with COPD exacerbations (p=0.008). Logistic regression models confirmed the association with rs3024791 (p = 0.007). Poisson regression models demonstrated association of multiple SFTPB SNPs with exacerbation rates: rs2118177 (p = 0.006), rs2304566 (p = 0.002), rs1130866 (p = 0.04), and rs3024791 (p = 0.002). Polymorphisms in EPHX1, GSTP1, TGFB1, and SERPINE2 did not demonstrate association with COPD exacerbations.
Variants in SFTPB are associated with COPD susceptibility and COPD exacerbation frequency.
PMCID: PMC2761762  PMID: 18550614
association analysis; COPD; exacerbations; genetics; surfactant protein B; single nucleotide polymorphisms
16.  The Effect of Lung Volume Reduction Surgery on Chronic Obstructive Pulmonary Disease Exacerbations 
Rationale: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known.
Objectives: To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT).
Methods: A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis.
Measurements and Main Results: There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV1 (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively).
Conclusions: LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.
Clinical trial registered with (NCT 00000606).
PMCID: PMC2204077  PMID: 17962632
COPD; LVRS; exacerbation
17.  Predicting Mortality and Healthcare Utilization with a Single Question 
Health Services Research  2005;40(4):1234-1246.
We compared single- and multi-item measures of general self-rated health (GSRH) to predict mortality and clinical events a large population of veteran patients.
Data Source/Study Setting
We analyzed prospective cohort data collected from 21,732 patients as part of the Veterans Affairs Ambulatory Care Quality Improvement Project (ACQUIP), a randomized controlled trial investigating quality-of-care interventions.
Study Design
We created an age-adjusted, logistic regression model for each predictor and outcome combination, and estimated the odds of events by response category of the GSRH question and compared the discriminative ability of the predictors by developing receiver operator characteristic curves and comparing the associated area under the curve (AUC)/c-statistic for the single- and multi-item measures.
Data Collection/Extraction Methods
All patients were sent a baseline assessment that included a multi-item measure of general health, the 36-item Medical Outcomes Study Short Form (SF-36), and an inventory of comorbid conditions. We compared the predictive and discriminative ability of the GSRH to the SF-36 physical component score (PCS), the mental component score (MCS), and the Seattle index of comorbidity (SIC). The GSRH is an item included in the SF-36, with the wording: “In general, would you say your health is: Excellent, Very Good, Good, Fair, Poor?”
Principal Findings
The GSRH, PCS, and SIC had comparable AUC for predicting mortality (AUC 0.74, 0.73, and 0.73, respectively); hospitalization (AUC 0.63, 0.64, and 0.60, respectively); and high outpatient use (AUC 0.61, 0.61, and 0.60, respectively). The MCS had statistically poorer discriminatory performance for mortality and hospitalization than any other other predictors (p<.001).
The GSRH response categories can be used to stratify patients with varying risks for adverse outcomes. Patients reporting “poor” health are at significantly greater odds of dying or requiring health care resources compared with their peers. The GSRH, collectable at the point of care, is comparable with longer instruments.
PMCID: PMC1361190  PMID: 16033502
Quality of life; mortality; hospitalization; outpatient; risk assessment
18.  Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease 
BMC Ophthalmology  2006;6:20.
Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients.
Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master (TradeMark). Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls.
Ten minutes after fluorescein installition, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 ± 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 ± 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 ± 52.83 ng/ml) compared with that of controls (mean = 40.64 ± 7.96 ng/ml), averaging a three-fold increase.
Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease.
PMCID: PMC1523366  PMID: 16729882
19.  Functional Status and Patient Satisfaction 
To determine the extent to which chronic illness and disease severity affect patient satisfaction with their primary care provider in general internal medicine clinics.
Cross-sectional mailed questionnaire study.
Primary care clinics at 7 Veterans Affairs medical centers.
Of 62,487 patients participating in the Ambulatory Care Quality Improvement Project, 35,383 (57%) returned an initial screening questionnaire and were subsequently sent a satisfaction questionnaire. Patients (N=21,689; 61%) who returned the Seattle Outpatient Satisfaction Survey (SOSQ) were included in the final analysis, representing 34% of the original sample.
The organizational score of the SOSQ measures satisfaction with health care services in the internal medicine clinic, and the humanistic scale measures patient satisfaction with the communication skills and humanistic qualities of the primary care physician. For ischemic heart disease (IHD), chronic obstructive pulmonary disease (COPD), and diabetes, patient ability to cope with their disease was more strongly associated with patient satisfaction than disease severity. Among IHD patients, improvement in ability to cope emotionally with their angina was associated with higher SOSQ organizational scores (standardized β=0.18; P<.001) but self-reported physical limitation due to angina was not (β=0.01; P=.65). Similarly, in COPD, improved ability to cope with dyspnea was associated with greater organizational scores (β=0.11; P<.001) but physical function was not (β=−0.03; P=.27). For diabetes, increased education was associated with improved organizational scores (β=0.31; P<.001) but improvement in symptom burden was not (β=0.03; P=.14). Similar results were seen with prediction of SOSQ humanistic scores.
Patient education and ability to cope with chronic conditions are more strongly associated with satisfaction with their primary care provider than disease severity. Further improvements in patient education and self-management may lead to improved satisfaction and quality of care.
PMCID: PMC1490111  PMID: 15963172
patient satisfaction; health services research; quality of care; questionnaire design; linear models
20.  Continuity of Care and Other Determinants of Patient Satisfaction with Primary Care 
The patient-clinician relationship is a central feature of primary care, and recent developments in the delivery of health care have tended to limit continuity of care. The objective of this study was to evaluate the extent to which continuity of care and other factors are related to patient satisfaction.
Cross-sectional, mailed questionnaire study.
Primary care clinics at 7 Veterans Affairs medical centers.
Patients (N=21,689) participating in the Ambulatory Care Quality Improvement Project who returned the baseline Seattle Outpatient Satisfaction Questionnaire (SOSQ).
We evaluated the association between self-reported continuity and satisfaction, after adjusting for characteristics of patients, clinics, and providers. The humanistic scale of the SOSQ measures patient satisfaction with communication skills and humanistic qualities of providers, whereas the organizational scale measures satisfaction with delivery of health care services. The mean adjusted humanistic score for patients who reported always seeing the same provider was 17.3 (95% confidence interval [CI], 15.5 to 19.1) points higher than for those who rarely saw the same provider. Similarly, the mean adjusted organizational score was 16.3 (95% CI, 14.5 to 18.1) points higher for patients who always saw the same provider compared to rarely. Demographic factors, socioeconomic status, health status, clinic site, and patient utilization of services were all associated with both the adjusted humanistic and organizational scores of the SOSQ.
Self-reported continuity of care is strongly associated with higher patient satisfaction. This suggests that improving continuity of care may improve patient satisfaction with providers as well as with their health care organization.
PMCID: PMC1490082  PMID: 15836525
patient satisfaction; health services research; quality of care; questionnaire design; linear models

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