Risk of lymphoma in autoimmune rheumatic conditions.
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Autoimmune Diseases↗
Biomedical subjects
Ann Clarke
Publications and source records attributed to Ann Clarke.
Accidental ingestions in children with peanut allergy.
BACKGROUND: Accidental exposure to peanut has been reported to occur frequently. Total avoidance of peanut is difficult because of its widespread use, manufacturing and labeling errors, utensil contamination, and label misinterpretation. OBJECTIVE: Given the apparent increased awareness of peanut allergy by both consumers and food manufacturers, we aimed to determine the current frequency of accidental exposures occurring in peanut allergic children in Quebec and to identify factors associated with exposure. METHODS: The parents of children with peanut allergy diagnosed at the Montreal Children's Hospital completed questionnaires about accidental exposure to peanut occurring over the period of the preceding year. Logistic regression was used to identify associated factors. RESULTS: Of 252 children, 62% were boys, with a mean age of 8.1 years (SD, 2.9). The mean age at diagnosis was 2.0 years (SD, 2.1). Thirty-five accidental exposures occurred in 29 children over a period of 244 patient-years, yielding an annual incidence rate of 14.3% (95% CI, 10.0% to 19.9%). Fifteen reactions were mild, 16 moderate, and 4 severe. Of 20 reactions that were moderate to severe, only 4 received epinephrine. Eighty percent of children attended schools prohibiting peanut, and only 1 accidental exposure occurred at school. No associated factors were identified. CONCLUSION: Accidental exposure to peanut occurs at a lower frequency than previously reported, but most reactions are managed inappropriately. CLINICAL IMPLICATIONS: Enhanced awareness, access to safer environments, and good food manufacturing practices may have contributed to a lower incidence of inadvertent peanut exposure, but a further reduction and better education on allergy management are desirable.
Adolescent↗
Malignancy and autoimmunity.
PURPOSE OF REVIEW: The association of cancer with autoimmune disease has been under investigation for several years. Reports have appeared suggesting increased cancer risk in autoimmune rheumatic diseases. Evidence has been accumulating recently in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and scleroderma/systemic sclerosis. This review focuses on recent publications regarding risk of cancer in these conditions. RECENT FINDINGS: Despite a lack of a strong association between rheumatoid arthritis and cancer overall, studies show an increased risk for the development of lymphoma in rheumatoid arthritis. There are data suggesting an increased risk for rheumatoid arthritis patients regarding lung cancer. In Sjogren's syndrome-related malignancies, most publications in the past year relate to non-Hodgkin's lymphomas, and suggest possible mechanisms driving the association. Data substantiate an increased risk of certain cancers in systemic lupus erythematosus; the risk appears to be most heightened for lymphoma. A recent cohort study examined cancer risk in scleroderma; the estimates were lower than previous studies had suggested, and the confidence intervals relatively imprecise, making a definitive conclusion difficult. SUMMARY: There have been several papers published related to cancer in the rheumatic diseases, particularly inflammatory arthritis, Sjogren's syndrome, systemic lupus erythematosus, and scleroderma/systemic sclerosis. Continuing interest in the association between autoimmune rheumatic diseases and malignancy is likely, given the potential impact in terms of understanding both rheumatic diseases and cancer.
Autoimmune Diseases↗
Bayesian modelling of imperfect ascertainment methods in cancer studies.
Tumour registry linkage, chart review and patient self-report are all commonly used ascertainment methods in cancer epidemiology. These methods are used for estimating the incidence or prevalence of different cancer types in a population, and for investigating the effects of possible risk factors for cancer. Tumour registry linkage is often treated as a gold standard, but in fact none of these methods is error free, and failure to adjust for imperfect ascertainment can lead to biased estimates. This is true both if the goal of the study is to estimate the properties of each ascertainment type, or if it is to estimate cancer incidence or prevalence from one or more of these methods. Although rarely applied in the literature to date, when cancer is ascertained by three or more methods, standard latent class models can be used to estimate cancer incidence or prevalence while adjusting for the estimated imperfect sensitivities and specificities of each ascertainment method. These models, however, do not account for variations in these properties across different cancer sites. To address this problem, we extend latent class methodology to include a hierarchical component, which accommodates different ascertainment properties across cancer sites. We apply our model to a data set of 169 lupus patients with three ascertainment methods and eight cancer types. This allows us to estimate the properties of each ascertainment method without assuming any to be a gold standard, and to calculate a standardized incidence ratio for cancer for lupus patients compared to the general population. As our data set is small, we also illustrate the effects as more data become available. We show that our model produces parameter estimates that are substantially different from the currently most popular method of ascertainment, which uses tumour registry data alone.
Bayes Theorem↗
Exploring the links between systemic lupus erythematosus and cancer.
For decades, concern has been mounting that individuals with systemic lupus erythematosus (SLE) have increased susceptibility to cancer. Recent data confirm that certain cancers, particularly hematologic, occur more frequently in SLE than in the general population. Numerous pathogenic mechanisms are possible, but hypotheses remain largely speculative. In particular, data are inadequate on how cancer risk in SLE may be related to medication exposures. To evaluate the impact of medication exposures on cancer risk in SLE, cooperative efforts of Systemic Lupus International Collaborating Clinics and Canadian Network for Improved Outcomes in Systemic Lupus are currently in progress. This should provide much-needed insight into the pathogenesis of the association between cancer and SLE.
Humans↗
A comparison of prospective and retrospective evaluations of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus.
OBJECTIVE: To evaluate the comparability of prospective and retrospective evaluations of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). METHODS: Consecutive patients meeting ACR criteria for SLE were enrolled prospectively in our cohort. Prospective SLICC/ACR DI scores were collected on the 134 cohort members who were observed in the cohort between 1993-1999. The last available prospective SLICC/ACR DI scores were compared to scores that were retrospectively assigned (for the corresponding time point) from chart review by a research nurse blinded to the prospective values. Intra- and inter-observer agreement was assessed. Kappa coefficients with 95% confidence intervals (CI) were determined. RESULTS: The kappa correlation coefficient for agreement between prospective versus retrospective total damage scores was 0.68 (95% CI 0.54-0.81). Moderate to very good agreement was also observed with respect to the 12 individual organ systems itemized in this damage index. Substantial agreement was found between assessments done by different research nurses and for repeat assessments done by the same research nurse. CONCLUSION: These data suggest good agreement between prospective and retrospective evaluations of the SLICC/ACR DI scores.
Adult↗
Nuclear factor kappa B-dependent activation of the antiapoptotic bfl-1 gene by the Epstein-Barr virus latent membrane protein 1 and activated CD40 receptor.
Suppression of the cellular apoptotic program by the oncogenic herpesvirus Epstein-Barr virus (EBV) is central to both the establishment of latent infection and the development of EBV-associated malignancies. We have previously shown that expression of the EBV latent membrane protein 1 (LMP1) in Burkitt's lymphoma cell lines leads to increased mRNA levels from the cellular antiapoptotic bfl-1 gene (also known as A1). Furthermore, ectopic expression of Bfl-1 in an EBV-positive cell line exhibiting a latency type 1 infection protects against apoptosis induced by growth factor deprivation (B. N. D'Souza, M. Rowe, and D. Walls, J. Virol. 74:6652-6658, 2000). We now report that LMP1 drives bfl-1 promoter activity through interactions with components of the tumor necrosis factor receptor (TNFR)/CD40 signaling pathway. We present evidence that this process is NF-kappa B dependent, involves the recruitment of TNFR-associated factor 2, and is mediated to a greater extent by the carboxyl-terminal activating region 2 (CTAR2) relative to the CTAR1 domain of LMP1. Activation of CD40 receptor also led to increased bfl-1 mRNA levels and an NF-kappa B-dependent increase in bfl-1 promoter activity in Burkitt's lymphoma-derived cell lines. We have delineated a 95-bp region of the promoter that functions as an LMP1-dependent transcriptional enhancer in this cellular context. This sequence contains a novel NF-kappa B-like binding motif that is essential for transactivation of bfl-1 by LMP1, CD40, and the NF-kappa B subunit protein p65. These findings highlight the role of LMP1 as a mediator of EBV-host cell interactions and may indicate an important route by which it exerts its cellular growth transforming properties.
Animals↗
A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome.
BACKGROUND: Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are no prospective data to support this approach to thromboprophylaxis. METHODS: We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin. RESULTS: A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8). CONCLUSIONS: High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.
Adult↗
Do traditional Gail model risk factors account for increased breast cancer in women with lupus?
OBJECTIVE: To determine to what extent the observed experience of breast cancer in a combined cohort of patients with systemic lupus erythematosus (SLE) could be explained by the profile of breast cancer risk factors. METHODS: Data were pooled from 2 centers, the Montreal General Hospital and the Feinberg School of Medicine at Northwestern University in Chicago. For each female cohort member, the probability of developing breast cancer during followup was estimated based on factors (including the individual's age, parity, age at first live birth, age of menarche, personal history of benign breast disease, and family history) using the Gail model, an established model for predicting breast cancer risk. The actual occurrence of cancer cases was determined by linkage with regional cancer registries. RESULTS: Of the 583 women in the combined cohort, 5 had been diagnosed with breast cancer prior to cohort entry, and 14 declined participation. In those remaining, 12 cases of breast cancer occurred compared to 5.6 predicted by the Gail model (standardized incidence ratio 2.1, 95% confidence interval: 1.1, 3.7). Thus, after controlling for risk factors, the incidence of breast cancer was elevated. CONCLUSION: Our data suggest that the risk of breast cancer in our SLE cohort is not completely explained by traditional factors found in the Gail model. Other factors, such as carcinogenic exposures (i.e., alkylating agents and immunosuppressive drugs) or the immunologic dysregulation of SLE itself, may be contributory.
Age Factors↗
Adherence to ophthalmologic monitoring for antimalarial toxicity in a lupus cohort.
OBJECTIVE: Antimalarial agents (hydroxychloroquine and chloroquine) are important in the treatment of various rheumatic diseases, including systemic lupus erythematosus (SLE). Although these agents may lead to ocular complications, little is known about adherence to policies for ophthalmologic monitoring. We investigated adherence to the 1996 American College of Rheumatology (ACR) guidelines (recommending yearly ophthalmologic assessments) at our clinic, and determined the factors associated with nonadherence. METHODS: Chart review of the Montreal General Hospital lupus clinic cohort. RESULTS: Of 195 subjects with at least one full year of antimalarial exposure during 1996-2001, 5 refused participation and data on ophthalmology monitoring was incomplete for 42. Of the remaining 148 patients, 47 (32%) had missed at least one annual ophthalmology assessment (were nonadherent) during the interval; almost half of these had missed </= 2 assessments. Nonadherence was present in 50% of the 52 patients who had been taking an antimalarial agent for </= 5 years. In adjusted logistic regression models, cumulative damage (measured by the Systemic Lupus International Collaborating Clinics/ACR Damage Index) and antimalarial exposure </= 5 years were predictive of nonadherence. Adjusted estimates indicated a 1.2-fold increase (95% CI 1.0, 1.5) in the odds of nonadherence for every point increase in the total Damage Index score. The adjusted OR for individuals exposed to an antimalarial for </= 5 years was 5.2 (95% CI 2.1, 13.8). CONCLUSION: Our results indicate incomplete adherence to ACR guidelines at our center. Because patients with higher Damage Index scores were more likely to have missed ophthalmology appointments, even after adjusting for pertinent covariates, it suggests that sicker patients may be more at risk of nonadherence. The association of nonadherence with duration of antimalarial exposure, while not surprising, is still an important reminder that adherence to ophthalmologic monitoring may decrease as risk for retinal toxicity is increasing.
Adult↗
Malignancy and systemic lupus erythematosus.
The association of malignancy with systemic lupus erythematosus (SLE) has been investigated for years. The findings of cohort studies lend support for an increased risk of malignancy in SLE but are difficult to interpret definitively. In addition, several cohort studies have suggested an increased risk of non-Hodgkin's lymphoma but with imprecise estimation. There is inadequate evidence for any conclusions about the risk of solid tumors in these patients. A multicenter international research effort is in progress to elucidate these issues and to establish the role of exposures such as cytotoxic or immunomodulatory therapy. The recommendations advocated for cancer screening policies and for minimizing known risk factors for cancer in the general population should not be neglected in persons with SLE.
Cohort Studies↗
Prevalence of factors influencing cancer risk in women with lupus: social habits, reproductive issues, and obesity.
OBJECTIVE: There is mounting evidence that hematological malignancies are increased in systemic lupus erythematosus (SLE), and the risk of certain solid tumors may also be increased. The pathogenesis may be different for the 2 processes: risk of hematological malignancies in SLE may be due to chronic lymphocyte stimulation, while risk of solid tumors may be influenced by factors such as obesity and reproductive habits. We aimed to determine prevalence in a lupus cohort of selected factors that influence the risk of cancer, and to compare this prevalence to that of the general population. METHODS: Subjects were women followed in the Montreal General Hospital Lupus Clinic. We administered a postal survey of factors known to be associated with lung and aerodigestive cancers (smoking, alcohol use) as well as factors associated with breast and gynecologic cancers (nulliparity, use of oral contraceptives, and hormone replacement therapy). For patients who had died or been lost to followup, data were abstracted from clinic records. Information about nonsteroidal antiinflammatory drug (NSAID) use (a potentially protective factor for colorectal cancer) was also collected. Obesity prevalence was established from the clinic database. Comparison figures were obtained from the 1996-1997 National Population Health Survey data for Quebec women and age adjusted, where possible. RESULTS: Compared to the general population, the lupus population had lower prevalence of current use of oral contraceptives, and greater prevalence of obesity and nulliparity. The average number of pack-years among smokers was also greater in the lupus cohort. CONCLUSION: Solid cancer incidence in SLE may be influenced by established cancer risk factors such as smoking, obesity, and reproductive history.
Adult↗
Effective recruitment and retention of older adults in physical activity research: PALS study.
OBJECTIVES: To develop strategies to recruit and retain inactive older adults into a physical activity program. METHODS: Names of 7378 older adults were obtained from 60 neighborhoods. Then, 6401 potential subjects were matched to telephone numbers and phoned. Subjects meeting the screening criteria were invited to join the program (n = 4209). Walk leaders and social support were used to enhance retention. RESULTS: Five hundred seventy-three subjects were recruited (260 intervention and 313 control). The respective participation rate was 12.6% (260/2056) and 14.5% (313/2153), with low attrition of 31.9% (83/260) and 24.6% (77/313). CONCLUSION: Effective recruitment and retention strategies were identified.
Aged↗
Does affluence affect allergy preparedness?
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Child↗