Screening for depression in chronic obstructive pulmonary disease.

Depression and chronic obstructive pulmonary disease (COPD) are major causes of disability. Identifying COPD patients at risk for depression would facilitate the alleviation of an important comorbidity conferring additional risk for poor outcomes. The purpose of this study was to determine the utility of a brief screening measure, the 15-item Geriatric Depression Scale (GDS-15), in detecting the mood disorders in persons with COPD. This is a cross-sectional study of 188 persons with COPD, stratified by age (65 and older versus less than 65) and COPD severity using Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging. Screening cut-points were empirically derived using threshold selection methods and receiver operating characteristic (ROC) curves were estimated. The GDS-15 was used as a screening measure and diagnoses of Major Depressive Disorder (MDD) or other mood disorders were determined using a "gold standard" standardized structured clinical interview. Of the 188 persons with COPD, 25% met criteria for any mood disorder and 11% met criteria for MDD. Optimal threshold estimations suggested a GDS cut score of 5, which yielded adequate sensitivity and specificity in detecting MDD (81% and 87%, respectively) and correctly classified 86% of participants. To detect the presence of any mood disorder, a cut score of 4 was suggested yielding sensitivity and specificity of 67% and 82%, respectively; correctly classifying 79%. These results suggest that mood disorders are relatively common among persons with COPD. The GDS-15 is a useful screening measure to identify patients at risk for depression.

Employment in multiple sclerosis. Exiting and re-entering the work force.

Multiple sclerosis (MS) is associated with significant economic burden and high rates of unemployment. This investigation evaluated patient and disease characteristics associated with work loss and work initiation using the NARCOMS patient registry. Patient and disease characteristics associated with transitions to unemployment or employment were evaluated cross-sectionally and prospectively over the course of two assessment periods (mean interval of 1.56 +/- 0.93 years). Eligible participants included 8,867 patients for the cross-sectional component, and 8,122 for longitudinal analyses. At Time 1 and Time 2 56-58 % of MS patients were not employed. At Time 1, unemployed participants more likely to have a progressive disease course, had a longer symptom duration, greater levels of disability as measured by the PDDS, and greater functional limitations across all domains of the performance scales (p < 0.0001 for all). At Time 2, increasing MS symptoms in the past 6 months increased the odds of becoming unemployed. In addition, specific problems in mobility, hand function, fatigue, and cognitive performance domains were associated with increased odds of becoming unemployed. Less severe problems in similar areas, including mobility, hand function, and cognitive functioning were also predictive of work initiation among patients not employed. MS is associated with high rates of unemployment. Specific physical and mental health limitations confer risk of employment cessation over time, as well as the likelihood of employment initiation. This study has implications for rehabilitation interventions to target specific MS related limitations that place patients at greatest risk for work status changes.

Longitudinal associations between MRI and cognitive changes in very early MS.

OBJECTIVES: Cognitive dysfunction in multiple sclerosis (MS) has been primarily examined in patients with advanced disease. Our objective was to study the longitudinal associations between brain magnetic resonance imaging (MRI) metrics and neuropsychological outcomes in patients with early MS. METHODS: Relapsing MS patients within 12 months of onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included percent brain volume changes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). A neuropsychological battery was performed annually. Mixed model regression measured time trends and associations between imaging and neuropsychological outcomes, adjusting for sex, age and education level. RESULTS: Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5 ± 4.9 months of disease onset. 11.6% of patients with baseline cognitive assessment met conservative criteria for cognitive impairment. Compared to placebo, riluzole had no significant effect on neuropsychological performance; thus, both groups were combined for the association analyses. Baseline T2LV predicted subsequent changes in PASAT (p=0.006) and SDMT (p=0.002) scores. Longitudinal changes of T2LV were associated with changes in CVLT-II (p<0.001). CONCLUSION: These findings suggest that cognitive impairment is relatively common in patients with very early MS. Baseline and longitudinal changes in the lesion load may be associated with some of the most frequently identified changes in cognitive function in MS.

Magnetic resonance imaging correlates of clinical outcomes in early multiple sclerosis.

OBJECTIVES: To study the association between changes in brain magnetic resonance imaging (MRI) and clinical outcomes in early MS. METHODS: MS patients within 12 months of onset were enrolled and followed up to 3 years. Clinical measures included Symbol Digit Modalities Test (SDMT), MS Functional Composite (MSFC) and low contrast letter acuity (LCLA). MRI outcomes included brain volume changes measured by SIENA and SIENAX normalized measurements [brain parenchymal volume (BPV), normal-appearing white and gray matter volume (NAWMV and GMV) and T2 lesion volume (T2LV)]. Mixed model regression measured time trends and associations between imaging and clinical outcome. RESULTS: Forty-three patients were enrolled within 7.5±4.9 months of onset. Baseline T2 lesion volume predicted subsequent changes in Paced Auditory Serial Addition Test (PASAT) (p=0.004), whereas baseline measures of atrophy including BPV, GMV, and NAWMV predicted longitudinal changes in MSFC (p=0.016, p=0.040, p=0.021, respectively) and Timed-25 Foot Walk (p<0.05). Each 1% decrease in SIENA was associated with 1.14 point decrease in SDMT score (p=0.03). Each 1% decrease in brain volume SIENA was associated with almost 1.5 letters decrease on LCLA (p=0.02). CONCLUSION: Measures of lesion volume and overall brain volume were associated with different long-term clinical outcome measures in early MS.

Validity of brief screening tools for cognitive impairment in rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To determine the validity of standardized screening assessments of cognitive functioning to detect neuropsychological impairment evaluated using a comprehensive battery in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: This is a cross-sectional study using a combined cohort of 139 persons with SLE and 82 persons with RA. Screening cut points were empirically derived using receiver operating characteristic curves and threshold selection methods. Screening measures included the Hopkins Verbal Learning Test-Revised (HVLT-R) learning and delayed recall indices and phonemic fluency, a composite measure of the 3 cognitive screening tests, and the Perceived Deficits Questionnaire-Short Form (PDQ-SF), a self-report measure of cognitive symptoms. A comprehensive neuropsychological battery was administered as the "gold standard" index of neuropsychological impairment. RESULTS: Rates of neuropsychological impairment were 27% and 15% for the SLE and RA cohorts, respectively. Optimal threshold estimations were derived for 5 screening techniques. The HVLT-R learning and phonemic fluency indices yielded the greatest sensitivity at 81%. The PDQ-SF yielded the lowest sensitivity at 52%. All measures were significantly associated with neuropsychological impairment after controlling for relevant sociodemographic covariates and depression. CONCLUSION: These results suggest that telephone-administered screening techniques may be useful measures to identify persons with neuropsychological impairment. Specifically, measures of phonemic fluency and verbal learning appeared to be most sensitive and least likely to misclassify impaired individuals as cognitively intact. Self-reported questionnaires may have relatively decreased sensitivity compared to standardized interviewer-administered cognitive measures.

Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. METHODS: Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. RESULTS: The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). CONCLUSION: These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk.

Cognitive functioning in multiple sclerosis.

In this article, the nature and course of cognitive dysfunction in MS are reviewed, particularly in the context of recent advances in our understanding of the diffuse nature of neuropathology in MS, and in the context of specific factors that may confer risk or protection for the development of cognitive impairment. In addition, assessment and screening approaches of MS-related cognitive dysfunction are discussed. MS is a condition not only restricted to the adult population, and this article includes a brief description of cognition in pediatric-onset MS. Finally, promising intervention approaches to treat cognitive problems in MS are summarized.

Using the Center for Epidemiologic Studies Depression Scale to screen for depression in systemic lupus erythematosus.

OBJECTIVE: Identifying persons with systemic lupus erythematosus (SLE) at risk for depression would facilitate the identification and treatment of an important comorbidity conferring additional risk for poor outcomes. The purpose of this study was to determine the utility of a brief screening measure, the Center for Epidemiologic Studies Depression Scale (CES-D), in detecting mood disorders in persons with SLE. METHODS: This cross-sectional study examined 150 persons with SLE. Screening cut points were empirically derived using threshold selection methods, and receiver operating characteristic curves were estimated. The empirically derived cut points of the CES-D were used as the screening measures and were compared to other commonly used CES-D cut points in addition to other commonly used methods to screen for depression. Diagnoses of major depressive disorder or other mood disorders were determined using a "gold standard" structured clinical interview. RESULTS: Of the 150 persons with SLE, 26% of subjects met criteria for any mood disorder and 17% met criteria for major depressive disorder. Optimal threshold estimations suggested a CES-D cut score of 24 and above, which yielded adequate sensitivity and specificity in detecting major depressive disorder (88% and 93%, respectively) and correctly classified 92% of participants. To detect the presence of any mood disorder, a cut score of 20 and above was suggested, yielding sensitivity and specificity of 87% and correctly classifying 87%. CONCLUSION: These results suggest the CES-D may be a useful screening measure to identify patients at risk for depression.

Cardiovascular and disease-related predictors of depression in systemic lupus erythematosus.

OBJECTIVE: Depression and cardiovascular disease are common and debilitating comorbidities associated with systemic lupus erythematosus (SLE). In this study, history of cardiovascular events, cardiovascular risk factors, and SLE disease-related factors were evaluated as longitudinal predictors of depression in a large cohort of patients with SLE. METHODS: Data were derived from 663 adult participants in the 2004-2008 Lupus Outcomes Study, who were followed for up to 5 annual interviews. Multivariate logistic regression analyses using generalized estimating equations were used to determine predictors of the development of increased depressive symptom severity over a 12-month period (Center for Epidemiologic Studies Depression Scale [CES-D] score of 23 or greater), yielding 2,224 paired observations. Predictors included sociodemographics, traditional cardiovascular risk factors (reported presence of heart disease, history of stroke or myocardial infarction, hypertension, hypercholesterolemia, diabetes mellitus, obesity, smoking status, and family history), and SLE-specific risk factors (glucocorticoid use, renal involvement, disease duration, and disease activity). RESULTS: The annual incidence of depression was 12% in this cohort. Multivariate predictors of new-onset depression included younger age (ages 20-39 years: odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.3-3.9; ages 40-59 years: OR 1.8, 95% CI 1.1-2.7), Hispanic/Latino ethnicity (OR 1.8, 95% CI 1.2-2.8), having some college education (OR 1.8, 95% CI 1.1-3.0), baseline CES-D score (OR per point 1.1, 95% CI 1.1-1.2), presence of diabetes mellitus (OR 1.8, 95% CI 1.1-2.8), and baseline SLE disease activity (OR 1.2, 95% CI 1.1-1.4). CONCLUSION: These results suggest that, in addition to known sociodemographic factors, the presence of diabetes mellitus and SLE disease activity may play a role in the development of depression in SLE.

Health-related quality of life is reduced in pediatric multiple sclerosis.

The health-related quality of life of children with multiple sclerosis was compared with that of healthy children and of those with other neurologic diseases. The Pediatric Quality of Life Inventory Version 4.0 was administered to children with multiple sclerosis and clinically isolated syndrome and their parents (proxy reporters) at the University of California, San Francisco (UCSF), Regional Pediatric Multiple Sclerosis Center. Scores were compared with those of siblings and to those of children seen at the UCSF Pediatric Muscular Dystrophy Association Center. After adjustment for age and sex, children with multiple sclerosis or clinically isolated syndrome (P = 0.003) and their parents (P = 0.001) reported worse overall health-related quality of life than their siblings. Although overall scores for those with early multiple sclerosis or clinically isolated syndrome were better than for children with neuromuscular disease, their self-reported psychosocial scores were similar. The main predictor of reduced self-reported health-related quality of life among children with multiple sclerosis or clinically isolated syndrome was greater neurologic disability, whereas parents reported worse scores for girls, older children, and those with longer disease duration. Although it is better than for children with chronic neuromuscular diseases, children with multiple sclerosis or clinically isolated syndrome have substantial reductions in health-related quality of life.

COPD and cognitive impairment: the role of hypoxemia and oxygen therapy.

BACKGROUND: several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy. METHODS: we used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV(1)); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking. RESULTS: COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64). Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases). Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048). Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001). CONCLUSION: COPD is a major risk factor for cognitive impairment. Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective. Health care providers should consider screening their COPD patients for cognitive impairment.

The impact of disability on depression among individuals with COPD.

BACKGROUND: Both disability and depression are common in COPD, but limited information is available on the time-ordered relationship between increases in disability and depression onset. METHODS: Subjects were members of a longitudinal cohort with self-reported physician-diagnosed COPD, emphysema, or chronic bronchitis. Data were collected through three annual structured telephone interviews (T1, T2, and T3). Depression was defined as a score >/= 4 on the Geriatric Depression Scale Short Form (S-GDS). Disability was measured with the Valued Life Activities (VLA) scale; three disability scores were calculated: percent of VLAs unable to perform, percent of VLAs affected (unable to perform or with some degree of difficulty), and mean VLA difficulty rating. Disability increases were defined as a 0.5 SD increase in disability score between T1 and T2. Multiple logistic regression analyses estimated the risk of T3 depression following a T1 to T2 disability increase for the total cohort and then excluding individuals who met the depression criterion at T1 or T2. RESULTS: Approximately 30% of subjects met the depression criterion each year. Eight percent to 19% experienced a T1 to T2 disability increase, depending on the disability measure. Including all cohort members and controlling for baseline S-GDS scores, T1 to T2 increases in disability yielded a significantly elevated risk of T3 depression (% affected odds ratio [OR] =3.6; 95% CI, [1.7, 7.7]; % unable OR = 6.1 [17, 21.8]; mean difficulty OR= 3.6 [1.7, 8.0]). Omitting individuals depressed at T1 or T2 yielded even stronger risk estimates for % unable (OR = 13.4 [2.0, 91.4]) and mean difficulty (OR = 3.9 [1.3, 11.8]). CONCLUSIONS: Increases in VLA disability are strongly predictive of the onset of depression.

Provision of preventive health care in systemic lupus erythematosus: data from a large observational cohort study.

INTRODUCTION: Cancer and infections are leading causes of mortality in systemic lupus erythematosus (SLE) after diseases of the circulatory system, and therefore preventing these complications is important. In this study, we examined two categories of preventive services in SLE: cancer surveillance (cervical, breast, and colon) and immunizations (influenza and pneumococcal). We compared the receipt of these services in SLE to the general population, and identified subgroups of patients who were less likely to receive these services. METHODS: We compared preventive services reported by insured women with SLE enrolled in the University of California, San Francisco Lupus Outcomes Study (n=685) to two representative samples derived from a statewide health interview survey, a general population sample (n=18,013) and a sample with non-rheumatic chronic conditions (n=4,515). In addition, using data from the cohort in both men and women (n=742), we applied multivariate regression analyses to determine whether characteristics of individuals (for example, sociodemographic and disease factors), health systems (for example, number of visits, involvement of generalists or rheumatologists in care, type of health insurance) or neighborhoods (neighborhood poverty) influenced the receipt of services. RESULTS: The receipt of preventive care in SLE was similar to both comparison samples. For cancer surveillance, 70% of eligible respondents reported receipt of cervical cancer screening and mammography, and 62% reported colon cancer screening. For immunizations, 59% of eligible respondents reported influenza immunization, and 60% reported pneumococcal immunization. In multivariate regression analyses, several factors were associated with a lower likelihood of receiving preventive services, including younger age and lower educational attainment. We did not observe any effects by neighborhood poverty. A higher number of physician visits and involvement of generalist providers in care was associated with a higher likelihood of receiving most services. CONCLUSIONS: Although receipt of cancer screening procedures and immunizations in our cohort was comparable to the general population, we observed significant variability by sociodemographic factors such as age and educational attainment. Further research is needed to identify the physician, patient or health system factors contributing to this observed variation in order to develop effective quality improvement interventions.

Relationships among anxiety, depression, and executive functioning in multiple sclerosis.

Anxiety is a common psychiatric symptom among patients with multiple sclerosis (MS), however compared to depression it is relatively under-studied. The relative contribution of anxiety and depression to cognitive functioning was evaluated among 77 persons with MS. Participants completed the Chicago Multiscale Depression Inventory, the State-Trait Anxiety Inventory, and neuropsychological measures of executive functioning. Regression analyses indicated that, although both depression and anxiety independently predicted performance on an index of executive functioning, anxiety was uniquely associated with cognitive functioning in MS, above and beyond depression. These results suggest that consideration of anxiety in the assessment and treatment of MS patients is warranted.

Depression, medication adherence, and service utilization in systemic lupus erythematosus.

OBJECTIVE: Forgetting to take medications is an important cause of nonadherence. This study evaluated factors associated with forgetting to take medications in a large cohort of persons with systemic lupus erythematosus (SLE) participating in the University of California, San Francisco Lupus Outcomes Study (LOS). Relationships among adherence problems and service utilization (outpatient visits, emergency department visits, and hospitalizations) were also evaluated. METHODS: The cohort consisted of 834 LOS participants who provided self-reported frequency of forgetting to take medications as directed. Predictors of adherence and service utilization patterns included self-reported sociodemographics, disease-related characteristics (e.g., disease activity, recent SLE flare), and mental health characteristics (Center for Epidemiologic Studies Depression Scale and cognitive function screen). Health care utilization patterns included the presence and quantity of visits to rheumatologists, primary care physicians, other care providers, emergency departments, and hospitalizations. RESULTS: Forty-six percent of the LOS cohort reported forgetting to take medications at least some of the time. Depressive symptom severity was a strong predictor of adherence difficulties (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02-1.05; P < 0.0001) after accounting for all other predictors. Persons reporting adherence difficulties had significantly greater numbers of outpatient rheumatology and primary care visits, and were more likely to visit the emergency department (OR 1.45, 95% CI 1.04-2.04; P = 0.03). CONCLUSION: Depression may be an important cause of medication adherence problems, and difficulties with adherence are significantly associated with high-cost service utilization, specifically emergency department visits. In an era of rapidly evolving treatments for lupus, identifying patients at risk for adherence problems may decrease medical expenditures and improve patient outcomes in SLE.

The role of neighborhood and individual socioeconomic status in outcomes of systemic lupus erythematosus.

OBJECTIVE: To determine if neighborhood socioeconomic status (SES) is independently related to physical and mental health outcomes in systemic lupus erythematosus (SLE). METHODS: Data derived from the first 3 waves of the Lupus Outcomes Study, a telephone survey of 957 patients with confirmed SLE diagnoses, recruited from clinical and non-clinical sources. Residential addresses were geocoded to U.S. Census block groups. Outcome measures included the Systemic Lupus Activity Questionnaire (SLAQ) score, a self-reported assessment of SLE symptoms; the Medical Outcomes Study Short Form-36 Health Survey physical functioning score; and Center for Epidemiologic Studies-Depression (CES-D) score of > or = 19 points. Multivariate analyses adjusted for race/ethnicity and other demographic and health-related covariates. RESULTS: After adjustment, lower individual SES, measured by education, household income, or poverty status, was associated with all outcomes. In models that did not include individual SES, low neighborhood SES (> 30% of residents in poverty) was also associated with poor outcomes. After adjustment for individual SES, demographic, and health-related covariates, only CES-D > or = 19 remained associated with neighborhood SES: 47% [95% confidence interval (CI) 38-56%] versus 35% (95% CI 32-37%). CONCLUSION: Individual SES is associated with physical and mental health outcomes in persons with SLE. Low neighborhood SES contributes independently to high levels of depressive symptoms. Future research should focus on mechanisms underlying these differences.

Cognitive predictors of response to treatment for depression in multiple sclerosis.

Cognitive impairment, particularly in the domain of executive functioning, has been demonstrated to predict poorer antidepressant medication treatment response. In this investigation, neuropsychological functioning was evaluated as a predictor of depression treatment response among 59 patients with multiple sclerosis. Performance on a Stroop task accounted for 28.7% of the variance in poorer pharmacologic antidepressant treatment response, as compared to less than 1% of the variance in two psychotherapy conditions. These results provide preliminary evidence to suggest that performance on neuropsychological measures may predict antidepressant treatment response in multiple sclerosis.