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E W Karlson

Publications and source records attributed to E W Karlson.

At least 19 recordsLinked to original sources

Cigarette smoking and autoimmune disease: what can we learn from epidemiology?

Cigarette smoking has been causally linked to the development of multiple autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Graves' hyperthyroidism, and primary biliary cirrhosis, among others. We review the known biologic effects of cigarette smoke, in particular its actions on the immune system, and the epidemiologic evidence associating smoking with increased risk of each of these autoimmune diseases. Interactions between cigarette smoking and genetic and immunologic factors, such as the human leukocyte antigen (HLA)-shared epitope, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and anti-double stranded DNA antibodies, may point to mechanisms in disease pathogenesis.

Arthritis, Rheumatoid↗

High sensitivity, specificity and predictive value of the Connective Tissue Disease Screening Questionnaire among urban African-American women.

The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen populations for SLE and other CTDs, has been validated in a predominantly Caucasian population with hospital-based controls. We aimed to test the performance characteristics of the CSQ in an urban, predominantly African-American population. The CSQ was administered by interview to women recruited for a study of environmental risk factors and SLE, including 99 cases with SLE validated by medical record review and 202 healthy controls recruited from the community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4% were non-Hispanic Caucasian. Controls were more likely to report African heritage than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and specificity was 91%. In this study, where the prevalence of SLE was 33%, predictive value of a positive CSQ was 82% and predictive value of a negative CSQ was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE in an urban, predominantly African-American population with community-based controls compared with a Caucasian population with hospital-based controls. These results suggest that the CSQ has adequate sensitivity and specificity and could be used in population studies to screen African-American women for SLE.

Adult↗

Validation of a Systemic Lupus Activity Questionnaire (SLAQ) for population studies.

The goal of this work was to develop an economical way of tracking disease activity for large groups of systemic lupus erythematosus (SLE) patients in clinical studies. A Systemic Lupus Activity Questionnaire (SLAQ) was developed to screen for possible disease activity using items from the Systemic Lupus Activity Measure (SLAM) and tested for its measurement properties. The SLAQ was completed by 93 SLE patients just prior to a scheduled visit. At the visit, a rheumatologist, blinded to SLAQ results, examined the subject and completed a SLAM. Associations among SLAQ, and SLAM (omitting laboratory items) and between individual items from each instrument were assessed with Pearson correlations. Correlations between pairs of instruments were compared using Student's t-tests. The mean score across all 24 SLAQ items was 11.5 (range 0-33); mean SLAM without labs was 3.0 (range 0-13). The SLAQ had a moderately high correlation with SLAM-nolab (r = 0.62, P < 0.0001). Correlations between patient-clinician matched pairs of items ranged from r = 0.06 to 0.71. Positive predictive values for the SLAQ ranged from 56 to 89% for detecting clinically significant disease activity. In studies of SLE, symptoms suggesting disease can be screened by self-report using the SLAQ and then verified by further evaluation.

Adult↗

Monoclonal gammopathy of undetermined significance and exposure to breast implants.

BACKGROUND: Animal studies and uncontrolled case series in humans have suggested a possible association between breast implant exposure and monoclonal gammopathy. OBJECTIVE: To assess whether there is an increased risk of monoclonal gammopathy in women with silicone breast implants, we conducted a retrospective study of women exposed to breast implants and matched nonexposed women nested within a prospective cohort study (the Nurses' Health Study). METHODS: We used serum protein electrophoresis and immunoglobulin subtype by immunofixation to test 288 women exposed to breast implants and 288 age-matched, nonexposed women who previously had provided a blood sample (1989-1990) for monoclonal proteins. RESULTS: Among the women exposed to breast implants, 5 had monoclonal gammopathy of undetermined significance (MGUS) compared with 4 women among those not exposed (odds ratio, 1.25; 95% confidence interval, 0.27-6.39). The distribution of isotypes was similar across exposure groups. The exposed women with MGUS tended to be older than the nonexposed women (mean age, 60.4 years vs 52.5 years, respectively; P =.03). None of the 9 women with MGUS had reported multiple myeloma or other hematologic malignancies up through 1996. CONCLUSIONS: We find little evidence to support a substantial increased risk of MGUS in women exposed to breast implants. Larger studies are needed to determine if a more modest relationship exists.

Age Factors↗

Variable effects of social support by race, economic status, and disease activity in systemic lupus erythematosus.

OBJECTIVE: Health status and disease activity in patients with systemic lupus erythematosus (SLE) and other chronic diseases are strongly associated with social support, which suggests that enhanced social support in medical care might improve SLE outcome. There has been little or no study on identifying patients for whom social support would be most beneficial. It would allow practitioners to enable social support more effectively as a complement to disease management. METHODS: A retrospective cohort (200 patients with SLE from 5 centers), balanced by race and insurance status, was studied in a cross sectional design. Demographic, clinical, socioeconomic, and psychosocial factors and disease outcomes [Systemic Lupus Activity Measure (SLAM), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR), SF-36] were measured. Using multivariate linear regression and ANOVA (outcome = SF-36 physical function, mental health), we examined the interaction between social support and patients' characteristics, including race, age, income, occupation, insurance, employment, education, and social network, and characteristics of the disease itself such as disease activity (SLAM) at diagnosis, damage (SLICC/ACR) at diagnosis, and comorbidity. RESULTS: In multivariate models, higher social support was significantly associated (p < 0.05) with better physical function when respondents were white, had income above poverty level, had Medicare or private insurance (vs Medicaid or no insurance), and had low disease activity at diagnosis. Social support was associated with better mental health, although there was no significant interaction between social support and other predictors of mental health. CONCLUSION: The data suggest that social support is beneficial for mental health for all groups, but has the greatest opportunity for influence among those already possessing social, economic, and health advantages.

Adult↗

Serologic evaluations of women exposed to breast implants.

OBJECTIVE: There continues to be uncertainty whether women with silicone breast implants experience activation of their immune system and show increased prevalence of serologic markers of connective tissue diseases. We conducted laboratory tests in a large number of women with and without breast implants, and in diabetic patients with presumed silicone exposure via insulin syringes. METHODS: Subjects were chosen from women enrolled in the run-in phase of the Women's Health Study (WHS, a randomized trial testing aspirin and vitamin E in preventing cardiovascular disease and cancer), and included 298 women without breast implants, 298 women with breast implants, and 52 diabetic patients diagnosed before age 30. Comparison groups were matched on age, race, date of blood provided to the WHS, and randomization status. We compared the proportion with abnormal results in 16 serologic tests among the 3 groups of women, stratifying by the matching factors. We also tested for monoclonal immunoglobulins by electrophoresis. RESULTS: For 14 of the 16 serologic tests, the proportions with abnormal results among the 3 groups of women were not significantly different. Of the remaining tests, C3 levels were decreased in 8 (2.7%) women without breast implants and 22 (7.4%) women with breast implants (p = 0.003). C4 levels were decreased in 31 (10.4%) women without breast implants and 48 (16.1%) women with breast implants (p = 0.03). Women without breast implants and diabetic patients did not differ significantly in the proportions having decreased C3 and C4 levels. Women with breast implants did not have higher frequency of monoclonal immunoglobulins detected by electrophoresis. CONCLUSION: We found little evidence for activation of the immune system in women with breast implants. The clinical significance of isolated reductions in C3 and C4 levels, in the absence of other abnormalities such as elevated levels of antinuclear antibody, is unknown.

Antibodies, Antinuclear↗

Association between clinical factors, socioeconomic status, and organ damage in recent onset systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence and socioeconomic and clinical predictors of early organ damage in a cohort of patients with systemic lupus erythematosus (SLE) of 2-7 years' duration randomly sampled at 5 centers and balanced by socioeconomic status and race. METHODS: The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index was measured in 200 patients who met the ACR criteria for SLE with a mean disease duration of 3.8 years. The SLICC/ACR scores for each organ system and the prevalence of damage within organ systems were assessed. Logistic regression analyses evaluated the simultaneous effects of age at diagnosis, disease duration, disease activity, and sociodemographic factors. RESULTS: Sixty-one percent of the patients had damage within 7 years of onset (mean 3.8 yrs). Neuropsychiatric (20.5%) and musculoskeletal (18.5%) systems were the most frequently involved, followed by renal (15.5%) and skin (12.5%) systems, all with median SLICC/ACR organ system scores of 1. In multivariate models, African-American race was associated with skin damage but not with damage in other specific organ systems. Socioeconomic status was not associated with organ system damage. Older age at diagnosis correlated with cardiovascular, musculoskeletal, gastrointestinal, ocular, and pulmonary damage. Clinical factors such as longer disease duration correlated with higher renal and cardiovascular damage, and greater disease activity at diagnosis of SLE correlated with greater renal, musculoskeletal, and pulmonary damage. CONCLUSION: There is evidence of organ system damage in SLE within a mean of 3.8 years after onset. We found little evidence for differences in early organ damage according to race or socioeconomic status. Damage to most organ systems was related to age at diagnosis of SLE and clinical factors such as disease duration.

Adult↗

Comparison of self-reported diagnosis of connective tissue disease with medical records in female health professionals: the Women's Health Cohort Study.

To compare self-report of connective tissue disease (CTD) with medical records, subjects were selected from 395,543 female health professionals with and without breast implants who reported CTD on mailed questionnaires from 1992 to 1995. The authors identified 220 women with breast implants (exposed) who self-reported CTD and a random sample of 879 women without breast implants (unexposed) who also self-reported CTD, matched by age and date of diagnosis. Medical records were reviewed using classification criteria from the American College of Rheumatology or other published criteria. After up to three requests and a telephone call, 27.7% of the women provided consent for medical record review. Exposed women appeared somewhat more likely (33.2% vs. 26.3%, p = 0.04) to provide consent. Using medical record reviews for 90% of the women who provided consent, confirmation rates of definite CTD were similar among the exposed and unexposed (22.7% vs. 24.0%, p = 0.83). This study demonstrates the difficulty of obtaining consent for medical record review of CTD reported to have occurred years ago in women with and without breast implants. Confirmation rates were low but were similar in exposed and unexposed. Despite the fact that the study had low participation rates, the data suggest that relative risk estimates for any definite CTD among women with breast implants compared with women without breast implants would be similar in analyses of self-reported or medical record-confirmed cases.

Adult↗

A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals.

OBJECTIVE: To study the association of cigarette smoking with risk of rheumatoid arthritis (RA), among 377,481 female health professionals in the Women's Health Cohort Study. METHODS: Subjects completed mailed questionnaires regarding demographics, health habits, including cigarette smoking history, and medical history, including RA diagnosis made by a physician and date of diagnosis. Of 7,697 women who self-reported RA, 3,416 reported seropositive RA. Cox proportional hazards regression models were used to retrospectively assess the associations of smoking intensity and duration with the risk of developing RA or seropositive RA. Cigarette smoking status was treated as a time-varying exposure in these regression models. RESULTS: In multivariate analyses controlling for age, race, education, age at menarche, pregnancy history, menopausal status, and postmenopausal hormone use, duration of smoking was associated with a significantly increased risk of both RA and seropositive RA (both P < 0.01 for trend), after adjusting for smoking intensity. Women who smoked > or =25 cigarettes/day for more than 20 years experienced a 39% increased risk of RA and 49% increased risk of seropositive RA. However, smoking intensity (number of cigarettes/day) was unrelated to risk of RA or seropositive RA (both P = 0.3 for trend), after adjusting for duration of smoking. CONCLUSION: Duration, but not intensity, of cigarette smoking is associated with a modest increased risk of RA in women.

Arthritis, Rheumatoid↗

Association of silicone breast implants with immunologic abnormalities: a prospective study.

PURPOSE: To study the possible association of silicone-breast-implant exposure and immunologic abnormalities within the Nurses' Health Study, an ongoing prospective cohort study of women. SUBJECTS AND METHODS: From this cohort, we randomly selected 200 women who had been exposed to silicone breast implants and who had never reported connective tissue diseases during 14 years of follow-up, and 500 age-matched, nonexposed women, including 100 with definite connective tissue diseases validated by medical record review, 100 with at least one symptom of a connective tissue disease, 100 with diabetes, and 200 healthy controls. Assays for antinuclear antibodies (ANA), including anti-dsDNA, anti-ssDNA, anti-Sm/RNP/Ro/La, and anti-Scl-70, rheumatoid factor, immunoglobulins, serum complement, and C-reactive protein level, and anticardiolipin, antithyroglobulin, antithyroid microsomal, and antisilicone antibodies were performed by standard techniques in blood samples collected in 1989 or 1990 before collection of silicone-breast-implant exposure data in 1992. RESULTS: ANA was positive (> or = 1:40) in 14% of women with silicone breast implants compared with 20% of healthy women (P = 0.11). Rheumatoid factor was positive (> or = 1:40) in 5% of women with silicone breast implants and 2% of healthy women (P = 0.16). Women with silicone breast implants had a significantly higher frequency of anti-ssDNA antibodies than healthy women (41% and 29%, P = 0.012). Duration of implant was associated with a higher frequency of anti-ssDNA antibodies (P = 0.03) but not with ANA or rheumatoid factor. No other significant differences in the frequencies of autoantibodies were observed in silicone breast implant-exposed women. Antisilicone antibodies were not found in any sample. CONCLUSION: We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance.

Adult↗

Determinants of cognitive performance in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) may have a variety of neuropsychiatric syndromes. Assessment of cognitive functioning for these patients is complicated by increased prevalence and disease severity among groups obtained lower scores on measures of cognitive functioning in normative national samples. Cognitive ability was quantified in a diverse cohort of patients with SLE and a demographically matched group of control participants. Hierarchical regression demonstrated a small increase (6%) in explained variation in cognitive functioning when presence of SLE was added to the equation derived from demographic variables. No significant interaction was found between race and disease. These results suggest that increased frequency of cognitive impairment in African Americans with SLE is due to the additive effects of psychosocial variables.

Adult↗

The relationship of socioeconomic status, race, and modifiable risk factors to outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: To study the relationship of race, socioeconomic status (SES), clinical factors, and psychosocial factors to outcomes in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective cohort was assembled, comprising 200 patients with SLE from 5 centers. This cohort was balanced in terms of race and SES. Patients provided information on socioeconomic factors, access to health care, nutrition, self-efficacy for disease management, health locus of control, social support, compliance, knowledge about SLE, and satisfaction with medical care. Outcome measures included disease activity (measured by the Systemic Lupus Activity Measure), damage (measured by the SLICC/ACR damage index), and health status (measured by the SF-36). RESULTS: In multivariate models that were controlled for race, SES, center, psychosocial factors, and clinical factors, lower self-efficacy for disease management (P < or = 0.0001), less social support (P < 0.005), and younger age at diagnosis (P < 0.007) were associated with greater disease activity. Older age at diagnosis (P < or = 0.0001), longer duration of SLE (P < or = 0.0001), poor nutrition (P < 0.002), and higher disease activity at diagnosis (P < 0.007) were associated with more damage. Lower self-efficacy for disease management was associated with worse physical function (P < or = 0.0001) and worse mental health status (P < or = 0.0001). CONCLUSION: Disease activity and health status were most strongly associated with potentially modifiable psychosocial factors such as self-efficacy for disease management. Cumulative organ damage was most highly associated with clinical factors such as age and duration of disease. None of the outcomes measured were associated with race. These results suggest that education and counseling, coordinated with medical care, might improve outcomes in patients with SLE.

Adult↗

Assessment of systemic lupus erythematosus disease activity by medical record review compared with direct standardized evaluation.

OBJECTIVE: Clinical studies of systemic lupus erythematosus (SLE) often necessitate assessment of previous disease activity, which is sometimes only possible by retrospective evaluation of information from the medical record. Using the Systemic Lupus Activity Measure (SLAM), the present study compared an assessment of disease activity obtained by chart abstraction with a direct clinical assessment. METHODS: A chart SLAM was obtained using information abstracted from the clinic notes of 46 patients with SLE who were being followed up at a referral center. Chart SLAM scores were compared with SLAM scores derived from an independent assessor's direct clinical evaluation. RESULTS: Direct SLAM and chart SLAM scores were correlated (r = 0.67 by Spearman's rank correlation, P = 0.0001). Chart review scores for disease activity tended to be lower, but to an inconsistent degree, reflecting both under- and overestimation of disease activity. The overall misclassification rate on a 3-category scale (mild, moderate, or severe activity) was 59%. CONCLUSION: Although chart SLAM scores were highly correlated with direct SLAM scores, misclassification of disease activity by chart review cannot be rectified. Thus, in research, medical record review should not be used as a proxy for the direct SLAM, nor should it be considered comparable with clinical assessments in the analysis of disease activity.

Adult↗

Past use of oral contraceptives and the risk of developing systemic lupus erythematosus.

OBJECTIVE: To examine the relationship between past use of oral contraceptives (OCs) and development of systemic lupus erythematosus (SLE). METHODS: Prospective cohort study of 121,645 women who were followed up every 2 years between 1976 and 1990 as part of the Nurses' Health Study. Women were classified as never users or past users of OCs based on self-report. Incidence of SLE was defined by 1) strict American College of Rheumatology (ACR) classification criteria (> or = 4 ACR criteria), 2) > or = 4 ACR criteria and any physician's diagnosis, 3) > or = 4 ACR criteria and diagnosis by an ACR-certified rheumatologist, 4) > or = 3 ACR criteria, or 5) diagnosis by a physician even if the patient did not meet the ACR criteria. RESULTS: Compared with never users of OCs, and after adjusting for age and ever use of postmenopausal hormones, the relative risk (95% confidence interval [95% CI]) for the incidence of SLE in the women who had definite cases of SLE (> or = 4 ACR criteria) (n = 99) was 1.4 (0.9-2.1) for past users of OCs. Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by an ACR member) (n = 58), the relative risk for past users compared with never users was 1.9 (95% CI 1.1-3.3). No relationship was observed between duration of OC use or time since first use and the risk of developing SLE. CONCLUSION: Past use of OCs was associated with a slightly increased risk of developing SLE. The decision to use hormonal contraception must be individualized, but the small absolute risk observed for the development of SLE in white women should not be a dominant factor in the decision.

Cohort Studies↗

Risk factors for early work disability in systemic lupus erythematosus: results from a multicenter study.

OBJECTIVE: To study the risk factors for early work disability in systemic lupus erythematosus (SLE). METHODS: A sample of 159 SLE patients who had been employed at some time since diagnosis was drawn from a multicenter study of outcome in SLE. Disease activity, organ damage, education, income, source of health insurance, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not working because of SLE. The outcome measure was current work status. Seven patients were excluded from the analysis because their choice not to work was unrelated to SLE. RESULTS: An average of 3.4 years after diagnosis, 40% had quit work completely, and job modification was substantial. Univariate analysis (chi-square and t-test) showed that significant predictors of early work disability included having a high school education or less, receiving Medicaid or having no health insurance, having a job which required more physical strength, having an income below poverty level, and having greater disease activity at diagnosis. In multivariate models, significant predictors were education level (P = 0.0004), higher physical demands of the job (P = 0.0028), and higher disease activity at diagnosis (P = 0.0078). Race, sex, cumulative organ damage at diagnosis, and disease duration were not significant. CONCLUSION: Early work disability in SLE is strongly associated with some sociodemographic factors that might be amenable to intervention.

Adult↗

Gender differences in patient preferences may underlie differential utilization of elective surgery.

PURPOSE: To study gender-specific preferences regarding timing of elective total joint replacement (TJR) surgery in patients with moderately severe osteoarthritis (OA) of the hip or knee. PATIENTS AND METHODS: Focus group discussions regarding TJR surgery were conducted among 18 women and among 12 men with moderately severe OA of the hip or knee. Discussions were tape recorded, transcribed, coded for themes, and evaluated semiquantitatively and qualitatively for gender differences. RESULTS: In general, men were more likely to choose surgery earlier in the disease than women and had higher expectations for surgical success. Women were more fearful of surgery. Women preferred to suffer arthritis pain rather than risk surgery, and indicated they would delay surgery to await better technology and to avoid disrupting caregiving roles for dependent spouses and others. CONCLUSION: Men and women differ in their willingness to accept continued functional decline, risks of surgery, and disruption of usual role. Gender differences may influence decisions regarding utilization of TJR.

Caregivers↗

Self-reported breast implants and connective-tissue diseases in female health professionals. A retrospective cohort study.

OBJECTIVE: To evaluate the association of breast implants with connective-tissue diseases. DESIGN AND PARTICIPANTS: Retrospective cohort study of 395,543 female health professionals who completed mailed questionnaires for potential participation in the Women's Health Study. A total of 10,830 women reported breast implants and 11,805 reported connective-tissue diseases between 1962 and 1991. Cox proportional hazards regression models were used in analyses. MAIN OUTCOME MEASURE: Self-reported connective-tissue diseases. RESULTS: Compared with women who did not report breast implants, the relative risk (RR) of the combined end point of any connective-tissue disease among those who reported breast implants was 1.24 (95% confidence interval, 1.08 to 1.41, P = .0015). With respect to the individual diseases, the finding for other connective-tissue diseases (including mixed) was statistically significant (P = .017), the findings for rheumatoid arthritis, Sjogren's syndrome, dermatomyositis or polymyositis, or scleroderma were of borderline statistical significance (.05 < P < .10), and the finding for systemic lupus erythematosus was not statistically significant (P = .44). There were no clear trends in RR with increasing duration of breast implants. CONCLUSION: These self-reported data from female health professionals are compatible with prior reports from other cohort studies that exclude a large hazard, but do suggest small increased risks of connective-tissue diseases among women with breast implants. The very large sample size makes chance an unlikely explanation for the results, but bias due to differential overreporting of connective-tissue diseases or selective participation by affected women with breast implants remains a plausible alternative explanation. The major contribution of this and other observational analytic studies has been to exclude large risks of connective-tissue diseases following breast implants.

Adult↗

Hair dye use and the risk of developing systemic lupus erythematosus.

OBJECTIVE: To investigate the role of hair dye use in the etiology of systemic lupus erythematosus (SLE). METHODS: Participants included 106,391 women enrolled in the Nurses' Health Study, a prospective cohort study. The subjects were ages 30-55 years in 1976, and were free from SLE and any other connective tissue disease at the time of enrollment. In 1976, 1978, 1980, and 1982, subjects were classified as never-users or ever-users of permanent hair dye, based on self-report. Incidence rates of SLE meeting American College of Rheumatology classification criteria were ascertained and confirmed by chart review. RESULTS: Compared with never-users of permanent hair dye, the age-adjusted relative risks (RR) for the development of SLE among ever-users (n = 85 cases) was 0.96 (95% confidence interval [95% CI] 0.63-1.47). Duration of hair dye use was not related to risk of SLE. Women with 15 or more years of use had no increased risk (RR = 0.92, 95% CI 0.46-1.83). There was no relationship between frequency of use or time since first use and risk of SLE. The results were similar when less stringent criteria for SLE were used. CONCLUSION: We found no evidence that permanent hair dye use, age at first use, frequency of use, or duration of use is associated with the development of SLE.

Adult↗