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S Bernatsky

Publications and source records attributed to S Bernatsky.

At least 19 recordsLinked to original sources

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study.

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.

Adult↗

Non-Hodgkin's lymphoma--meta-analyses of the effects of corticosteroids and non-steroidal anti-inflammatories.

OBJECTIVE: Recent research has focused on the effects of corticosteroids and non-steroidal anti-inflammatory drugs/agents (NSAIDs) on non-Hodgkin's lymphoma (NHL) risk, with inconclusive results. We conducted meta-analyses of data published to date, to ascertain the over-all association between NHL and corticosteroid use, and between NHL and NSAID use. METHODS: Literature searches were performed to find studies assessing the effects of corticosteroids and/or NSAIDs on NHL risk. We analysed nine case-control studies and one cohort study of the effect of corticosteroids and/or NSAIDs on NHL risk. We performed a formal meta-analysis using summary measures from these studies. RESULTS: The studies contributed 6897 NHL cases and 8881 controls for the corticosteroid analyses, and 5794 NHL cases and 34,707 controls for the NSAID analyses. There was no heterogeneity of the odds ratio (OR) estimates. The overall OR for the effect of corticosteroid exposure on NHL occurrence was not suggestive of an increased risk [OR 1.09, 95% confidence interval (CI) 0.96-1.24]. Similarly, the OR for the effect of NSAIDs on NHL occurrence did not support an increased risk (OR 0.93, 95% CI 0.74-1.14). CONCLUSIONS: Our meta-analyses suggest little evidence that corticosteroid or NSAID exposures are themselves risk factors for NHL. Early data linking corticosteroids and/or NSAIDs with NHL may reflect an underlying increased risk of lymphoma in patient populations that use these medications (i.e. autoimmune diseases such as rheumatoid arthritis), and may point to the importance of disease activity in driving NHL risk in these populations.

Aged↗

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Adolescent↗

Headache, Raynaud's syndrome and serotonin receptor agonists in systemic lupus erythematosus.

There are potential concerns regarding serotonin receptor agonists in SLE patients with migraine, particularly patients with concomitant Raynaud's syndrome. We estimated the prevalence of lupus-related headache and Raynaud's syndrome in the Montreal General Hospital SLE clinic cohort and evaluated the relationship between these two variables in multivariable logistic regression models, controlling for age, sex, race, SLE duration and the presence of lupus anticoagulant and antibodies to cardiolipin and beta2 glycoprotein I. We also assessed, through chart review in those individuals with both Raynaud's syndrome and migraine, a history of serotonin receptor agonist use, and any associated worsening vasospasm. Based on Systemic Lupus Activity Measure (SLAM) scores, the cumulative incidence of lupus-related headache in our sample (n = 391) was 46.1%; the prevalence of Raynaud's syndrome was 49.4%. The adjusted odds ratio (OR) for lupus-related headache and Raynaud's syndrome was 1.7 (95% CI 1.1, 2.5). In addition, there was a strong independent relationship between headache and anti-beta2 glycoprotein I antibodies (adjusted OR 5.6 [95% CI 1.8, 17.0]). The data from our chart review suggest that careful use of serotonin receptor agonists in patients with both Raynaud's syndrome and migraines may be undertaken, although caution would necessitate that these agents not be used in individuals with very severe Raynaud's (eg, digital ulcerations, and so on).

Adult↗

A comparison of damage accrual across different calendar periods in systemic lupus erythematosus patients.

Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n=100) and the second between 1989 and 1999 (cohort #2, n=51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.

Adrenal Cortex Hormones↗

Mortality related to cerebrovascular disease in systemic lupus erythematosus.

The objective of this study was to examine mortality rates related to cerebrovascular disease in systemic lupus erythematosus (SLE) compared to the general population. Our sample was a multisite Canadian SLE cohort (10 centres, n = 2688 patients). Deaths due to cerebrovascular disease were ascertained by vital statistics registry linkage using ICD diagnostic codes. Standardized mortality ratio (SMR, ratio of deaths observed to expected) estimates were calculated. The total SMR for death due to cerebrovascular disease was 2.0 (95% confidence interval [CI] 1.0, 3.7). When considering specific types of events, the category with the greatest increased risk was that of ill-defined cerebrovascular events (SMR 44.9 95% CI 9.3, 131.3) and other cerebrovascular disease (SMR 8.4, 95% CI 2.3, 21.6). Deaths due to cerebral infarctions appeared to be less common than hemorrhages and other types of cerebrovascular events. Our data suggest an increase in mortality related to cerebrovascular disease in SLE patients compared to the general population. The large increase in ill-defined cerebrovascular events may represent cases of cerebral vasculitis or other rare forms of nervous system disease; alternately, it may reflect diagnostic uncertainty regarding the etiology of some clinical presentations in SLE patients. The suggestion that more deaths are attributed to cerebral hemorrhage, as opposed to infarction, indicates that inherent or iatrogenic factors (eg, thrombocytopenia or anticoagulation) may be important. In view of the paucity of large-scale studies of mortality attributed to neuropsychiatric outcomes in SLE, our findings highlight the need for additional research in large SLE cohorts.

Adolescent↗

A randomized clinical trial of an individualized home-based exercise programme for women with fibromyalgia.

OBJECTIVE: To determine the efficacy of a 12-week individualized home-based exercise programme on physical functioning, pain severity and psychological distress for women with fibromyalgia (FM). METHODS: Seventy-nine women with a primary diagnosis of FM were randomized to a 12-week individualized home-based moderate-intensity exercise programme or to a usual care control group. Outcomes were functional capacity (Fibromyalgia Impact Questionnaire), pain severity and psychological distress. Outcomes were measured at study entry, at the end of the 12-week intervention, and at 3 and 9 months following completion of the intervention. RESULTS: On the basis of intention-to-treat analyses, a significant improvement in functional capacity at 3 and 9 months following treatment for participants in the exercise group who were more functionally disabled at study entry was observed. At both 3 and 9 months post-treatment, the mean estimated benefit of the intervention was more than 10 points [-12.3 (95% CI, -21.9 to -2.8); -10.8 (95% CI, -21.5 to -0.2)]. Compared with the control group, statistically significant improvements in upper body pain were evident in the exercise group at post-treatment. These between-group differences in upper body pain were maintained at 3 and 9 months post-treatment. No statistically significant group differences on lower body pain and psychological distress were found. CONCLUSIONS: Home-based exercise, a relatively low-cost treatment modality, has the potential to improve important health outcomes in FM.

Adult↗

Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis.

OBJECTIVE: To assess the risk of hospitalization for congestive heart failure (CHF) associated with the use of disease-modifying anti-rheumatic drugs (DMARDs) and other medications used in RA. METHODS: We used a case-control design nested within an administrative database cohort of patients with rheumatoid arthritis (RA) who were dispensed a DMARD between September 1998 and December 2001. Subjects identified with a prior history of CHF were excluded. For each hospitalized case of CHF identified during follow-up, 10 controls matched on age and time were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of hospitalizations for CHF associated with the current use of specific drugs, adjusted for sex and co-morbidity. RESULTS: The cohort included 41 885 patients; 75% were women, with an average age at cohort entry of 51 yr. During follow-up, 520 hospitalizations for CHF occurred, for a rate of 10.1 per 1000 per year. The adjusted RR of CHF for current use of any DMARD was 0.7 (95% CI 0.6-0.9) relative to no current use. By DMARD category, there was evidence of a beneficial effect for both tumour necrosis factor-alpha antagonists (RR 0.5, 95% CI 0.2-0.9) and methotrexate monotherapy (RR 0.8, 95% CI 0.6-1.0). For non-DMARD medications, the rate of CHF was not clearly increased or decreased, except for COX-2 inhibitors. The data suggested an increased risk of CHF with rofecoxib (RR 1.3, 95% CI 1.0-3.1) and a decreased risk of CHF with celecoxib (RR 0.6, 95% CI 0.4, 1.0). CONCLUSIONS: The use of DMARDs was associated with a reduction in the risk of hospitalizations for CHF in this RA cohort. The increased risk with rofecoxib alongside a decreased risk with celecoxib suggests the absence of a class effect with respect to COX-II inhibitors for some types of cardiovascular morbidity.

Adult↗

Co-morbidity and physician use in fibromyalgia.

OBJECTIVE: To describe comorbidity in women with FM, and to examine the effects of different types of comorbidity on physician use. METHODS: Women (n = 180) with primary FM were evaluated at baseline and 6 months later for self-reported health resource use and covariates. Reported comorbidity was classified into 4 categories: medical, psychiatric, "functional", and unknown. The category for "functional" conditions included disorders that have been classified by previous authors as medically unexplained symptoms such as the irritable bowel and chronic fatigue syndromes. Logistic regression models were developed to examine associations between types of comorbidity and physician use. RESULTS: Comorbid conditions were reported by over 90% of the sample. Total number of comorbid complaints was associated with high number of physician visits. In logistic regression models (controlling for age, ethnicity, education, disability, pain, and psychological vulnerability) medical comorbidity was a much stronger determinant of high number of physician visits than was "functional" comorbidity. CONCLUSIONS: Comorbidity with other disorders, both functional and medical, was high in this sample. Medical and psychiatric comorbidity were stronger determinants of high physician use than "functional" comorbidity.

Canada↗

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Adult↗

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

Adult↗

Factors associated with abnormal Pap results in systemic lupus erythematosus.

OBJECTIVE: Previous studies have suggested that women with systemic lupus erythematosus (SLE) are at greater risk for cervical dysplasia than are women in the general population. However, the factors associated with abnormal Pap test results in SLE have not been well studied. We therefore aimed to determine the factors associated with lifetime occurrence of an abnormal Pap test in women with SLE, and the influence of immunosuppressive exposure on the odds of abnormal Pap test results occurring after diagnosis of SLE. METHODS: Data were pooled from SLE cohorts from three centres. Self-report data were available on smoking, reproductive history, use of oral contraceptives (OC), history of sexually transmitted diseases (STDs) and whether the subjects had had cervical dysplasia on Pap testing. Logistic regression was used to examine the effect of these variables on the lifetime odds of cervical dysplasia. We then generated the adjusted odds ratio (OR) for the effect of immunosuppressive exposure on cervical dysplasia occurring after diagnosis of SLE. RESULTS: History of STDs and use of OCs were positively associated with reports of cervical dysplasia in adjusted analyses. The ORs for the effect of immunosuppressives on abnormal Pap test occurrence (adjusted for race, age, smoking, nulliparity, OC use and history of STDs) after diagnosis of SLE was 1.6 (95% CI 1.0, 2.7). CONCLUSIONS: A history of STDs and use of OCs were associated with abnormal Pap reports in this SLE sample. Immunosuppressive exposure may confer further risk to women with SLE.

Adult↗

Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus.

OBJECTIVES: To determine if breast cancer risk in women with SLE is modified by a history of exposure to hormone replacement therapy (HRT) or oral contraceptives (OC), after adjusting for other risk factors. METHODS: Data were pooled from SLE cohorts at three centres. For each female cohort member (n = 871), the probability of developing breast cancer was estimated from factors (age, parity, age at first live birth, age of menarche, personal history of benign breast disease, family history) in the Gail model, an established tool for predicting breast cancer risk. From these probabilities, the expected number of breast cancers for the cohort was estimated. Actual occurrence of cases was determined by linkage with regional cancer registries. Standardized incidence ratios (SIRs; ratio of cancers observed to expected) were calculated, with subgroup analyses according to HRT and OC exposure. RESULTS: In the cohort, 15 breast cancers occurred vs 7.2 predicted [SIR 2.1, 95% confidence interval (CI) 1.1, 3.5]. When controlling for Gail model risk factors, estimates were similar for women never exposed to HRT vs those exposed to HRT. Adjusted SIR estimates appeared similar also for women exposed or not exposed to OC. CONCLUSIONS: Although not definitive, the data suggest that the breast cancer experience in this sample is not completely explained by factors such as reproductive and family history, or by exogenous hormonal exposures. Other determinants, including medication exposures or genetic factors (possibly related to oestrogen receptors or metabolism) may be important. Variations in these factors might explain why an elevated risk of breast cancer has not been apparent in all SLE populations.

Adult↗

Medication non-adherence in women with fibromyalgia.

OBJECTIVE: To identify the determinants of medication non-adherence in women with fibromyalgia (FM). METHODS: Participants included 10 rheumatologists and 127 women recruited from tertiary care hospitals and the community. Demographic, clinical and psychosocial characteristics and patient-physician discordance were assessed at the baseline visit. Non-adherence was assessed 2 weeks later. Multivariable generalized estimating equations were used to identify determinants of non-adherence to medication. RESULTS: The average age of the women was 50.4 (s.d. 10.5) yr and the mean disability score was 60.3 (16.0) yr. Sixty (47.2%) women were non-adherent to medication; 20 (33.3%) of these were intentionally non-adherent, 24 (40.0%) were unintentionally non-adherent, and the remaining subjects were both. Overall non-adherence was predicted by higher patient-physician discordance. Unintentional non-adherence was predicted by community subjects, not being under a rheumatologist's care, less disease activity, less use of instrumental coping, and higher patient-physician discordance. Intentional non-adherence was predicted by shorter duration under a rheumatologist's care and higher patient-physician discordance. CONCLUSION: The therapeutic relationship, in addition to clinical and psychosocial characteristics, influenced non-adherence to medication.

Adaptation, Psychological↗

Breast cancer stage at time of detection in women with systemic lupus erythematosus.

Mounting evidence suggests an increased cancer risk in several autoimmune diseases, including systemic lupus erythematosus (SLE). However, greater scrutiny for cancer in subjects with chronic disease (compared to the general population) might explain this apparent association. If so, one would expect cancers in SLE to be diagnosed at earlier stages than in the general population. This might be particularly evident in cancers where screening is available, such as breast cancer. We linked the University of Pittsburgh lupus cohort with the Pennsylvania Cancer Registry to determine the frequency distribution for stage at diagnosis of invasive breast cancers in the SLE subjects. Data on staging of cancers occurring in the general population of Pennsylvania were obtained from The US Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. A lower percentage of women with SLE presented with localized breast cancer (nine of the 16, 56.2%) compared to the general population of women (63.5%). Although not definitive, this evidence suggests that cancers in SLE are not necessarily diagnosed at earlier stages than in the general population.

Adult↗