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S Manzi

Publications and source records attributed to S Manzi.

At least 19 recordsLinked to original sources
PubMed2007

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↗
PubMed2006

Association of a common interferon regulatory factor 5 (IRF5) variant with increased risk of systemic lupus erythematosus (SLE).

Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors that control the transactivation of type I interferon system-related genes, as well as the expression of several other genes involved in immune response, cell signalling, cell cycle control and apoptosis. Two recent studies reported a significant association between the IRF5/rs2004640 T allele and systemic lupus erythematosus (SLE). The purpose of this study was to determine whether the reported rs2004640 T allele association could be replicated in our independent SLE case-control sample. We genotyped DNA samples from 370 white SLE-affected female subjects and 462 white healthy female controls using the TaqMan Assay-on-Demand for rs2004640, and performed a case-control genetic association analysis. Frequency of the rs2004640 T allele was significantly higher in cases than in controls (56.5% vs. 50%; P= 0.008). The odds ratio for T allele carriers was 1.68 (95% CI: 1.20 - 2.34; P= 0.003). Our results in an independent case-control sample confirm the robust association of the IRF5/rs2004640 T allele with SLE risk, and further support the relevance of the type I interferon system in the pathogenesis of SLE and autoimmunity.

Adolescent↗
PubMed2006

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↗
PubMed2005

Disease damage and low bone mineral density: an analysis of women with systemic lupus erythematosus ever and never receiving corticosteroids.

OBJECTIVES: To evaluate the relationship between disease damage and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted among 307 women with SLE. Patients attended a single clinic visit that included an interview, physical examination, laboratory testing and BMD measurements (hip and/or lumbar spine). Women were stratified by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology cumulative disease damage index (SDI) > or =1 (Damage) vs SDI=0 (No Damage), and prior use of corticosteroids (CS), yielding four groups: (1) Damage/CS(+) (n=138), (2) Damage/CS(-) (n=23), (3) no Damage/CS(-) (n=100), and (4) no Damage/CS(-) (n=46). RESULTS: Mean age at SLE diagnosis was 32.7 +/- 11.8 yr, 24.4% were African American, 65.0% were premenopausal, and mean SDI +/- S.D. was 1.3 +/- 1.8. In the unadjusted and adjusted models controlling for significant univariate risk factors for osteoporosis, the reference group (Group 1) had significantly lower mean BMD T-scores at the hip and lumbar spine than groups having no disease damage (Groups 3 and 4) independent of CS use status. Similar hip and lumbar spine mean BMD T-scores were observed in women with disease damage with and without CS exposure (Groups 1 and 2). CONCLUSIONS: Women with SLE having disease damage and no CS use had BMD T-scores at the hip and lumbar spine similar to those of women with disease damage and prior CS use. These findings suggest an association between disease damage and lower BMD T-scores in women with SLE.

Adrenal Cortex Hormones↗
PubMed2005

Minor physical anomalies are not increased in the offspring of mothers with systemic lupus erythematosus.

OBJECTIVE: To determine the incidence and type of minor physical anomalies (MPAs) in infants born to mothers with systemic lupus erythematosus (SLE). METHODS: Each trimester, pregnant women with SLE were assessed for disease activity, prescribed drug use, and exposure to tobacco, alcohol, and illicit drugs through a self reported questionnaire. Infant examinations were performed on 30/39 (77%) live births in women with SLE and the incidence of MPAs determined. RESULTS: 2/30 (7%) patients had three or more MPAs; 4 (13%) had two; 7 (23%) had one; and 17 (57%) had none. One in three women reported alcohol, tobacco, and illicit drug use. Facial anomalies were the most common MPAs. The relative risk and 95% confidence interval for any MPA were 2.05 (0.99 to 4.26) for tobacco use; 1.95 (0.92 to 4.11) for alcohol use; 1.36 (0.165 to 11.23) for maternal disease flare; 0.63 (0.27 to 1.47) for prednisone use; and 0.72 (0.21 to 2.44) for aspirin use. CONCLUSION: 13/30 (43%) infants had minor anomalies-a similar incidence to that of the general population. Counselling for preventable self reported exposure is advisable in addition to counselling specifically for lupus management during pregnancy.

Acute Disease↗
PubMed2005

The systemic lupus erythematosus tri-nation study: longitudinal changes in physical and mental well-being.

OBJECTIVE: We have shown that SLE patients in Canada and the UK incurred 20% and 13% lower health costs than those in the US, respectively, but did not experience worse outcomes as expressed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We now compare change in quality of life in these patients. PATIENTS AND METHODS: Seven hundred and fifteen SLE patients (Canada 231, US 269, UK 215) completed the SF-36 annually over four years. The annual change in the SF-36 Physical and Mental Component Summary (PCS and MCS) scores over the course of the study were summarized by estimating a linear trend for each individual patient using hierarchical modelling. Cross-country comparison of the slopes in the PCS and MCS scores was then performed using simultaneous regressions. RESULTS: The estimated mean annual changes (95% credible interval [CrI]) in the PCS scores in Canada, the US, and the UK were 0.18 (-0.07, 0.43), -0.05 (-0.27, 0.17), and 0.03 (-0.20, 0.27), respectively; the mean annual changes in the MCS scores were 0.15 (-0.04, 0.34), 0.23 (0.09, 0.37), and 0.08 (-0.10, 0.27), respectively. Regression results showed that the mean annual changes in PCS and MCS scores did not substantially differ across countries. CONCLUSION: Quality of life remained stable across countries. Despite Canadian and British patients incurring lower health costs, on average, patients experienced similar changes in physical and mental well-being.

Adult↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2004

The systemic lupus erythematosus Tri-nation Study: absence of a link between health resource use and health outcome.

OBJECTIVE: Health consumption and health status in SLE in three countries with different health funding structures were compared. METHODS: Seven hundred and fifteen SLE patients (Canada 231, USA 269, UK 215) were surveyed semi-annually over 4 yr for health resource utilization and health status. Cross-country comparisons of (i) cumulative health expenditure (calculated by applying 2002 Canadian prices to resources in all countries) and (ii) disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, SLICC/ACR DI) at study conclusion were performed after adjustment. Missing expenditure and damage data were managed through multiple imputation using best predictive regressions with all available data from all patients as potential covariates. RESULTS: Four hundred and eighty-five patients provided data at study entry and conclusion and at least four resource questionnaires (Canada 162, USA 157, UK 166); 41 died (Canada 13, USA 18, UK 10); 189 withdrew, were lost to follow-up or provided data at entry and conclusion but fewer than four resource questionnaires (Canada 56, USA 94, UK 39). At conclusion, after imputation, in Canada, the USA and the UK respectively, mean cumulative costs per patient over 4 yr [95% confidence interval (CI)] were $15,845 (13,509, 18,182), $20,244 (17,764, 22,724) and $17,647 (15,557, 19,737) and mean changes in SLICC/ACR DI were 0.49 (0.39, 0.60), 0.63 (0.52, 0.74) and 0.48 (0.39, 0.57). After adjustment for baseline differences, on average (95% CI), Canadian and British patients utilized 20% (8%, 32%) and 13% (1%, 24%) less resources than patients in the USA respectively, but experienced similar health outcomes. CONCLUSION: Despite patients in the USA incurring higher health expenditures, they did not experience superior health outcomes.

Adult↗
PubMed2004

Adsorption of a multicomponent mixture of gases with multisite occupancy.

In this paper, we present a study of the adsorption of multicomponent mixtures with multisite occupancy. The transfer-matrix technique is used to analyze the one-dimensional binary mixtures for interacting systems. A general expression for the characteristic polynomial is derived. Extension of the treatment to a higher dimension is also presented by using the mean-field Bragg-Williams approximation, transfer-matrix calculations, and Monte Carlo simulation. Partial and total isotherms are obtained for the dimer-trimer mixture where a different order appears.

Journal Article↗
PubMed2004

New insights into complement: a mediator of injury and marker of disease activity in systemic lupus erythematosus.

Studies performed during the past several decades have demonstrated a role for the complement system in both the etiology and pathogenesis of systemic lupus erythematosus (SLE). However the specifically defective molecular and cellular pathways responsible for the disease and its complications have generally not been identified. In this report, we describe two recent advances in complement pathobiology that highlight future directions for promising investigation toward enhancing our capacity to diagnose SLE, to monitor activity of the disease, and to identify molecular and cellular defects in SLE that can be targeted by therapeutic inhibitors of complement activation. In the first example, we describe recently developed assays to detect erythrocyte C4d and complement receptor 1 for diagnosis and monitoring of disease activity in SLE. In the second example, we describe a recently discovered role for complement in mediating fetal loss in antiphospholipid syndrome and discuss the potential for this observation to facilitate identification and development of complement based biomarkers to predict poor fetal outcome in pregnant patients with SLE. These two examples are meant to underscore the importance of complement in the etiology and pathogenesis of SLE and its complications, and to stress the need for further investigation focused on the link between the complement system and SLE.

Biomarkers↗
PubMed2004

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↗
PubMed2004

Review of ACR hematologic criteria in systemic lupus erythematosus.

We have conducted a thorough literature review to evaluate the relative value of the hematologic criterion in making a diagnosis of systemic lupus erythematosus (SLE), its clinical relevance, and its prognostic significance. In the updated 1982 ACR criteria, the presence of one or more of the four elements: 1) hemolytic anemia (with reticulocytosis); 2) leukopenia (<4000/microL on two or more occasions); 3) lymphopenia (< 1500/microL on two or more occasions); or 4) thrombocytopenia (< 100,000/microL in the absence of offending drugs) is now considered as a single hematologic disorder. The sensitivity and specificity of the individual elements of the hematologic criterion range from 18 to 46% and 89 to 99%, respectively. The accuracy of the hematologic criterion requires proper interpretation. For example, many studies reported the presence of anemia that was not clearly defined and likely included anemia from etiologies other than hemolytic anemia, thereby causing an overestimation of the prevalence. In addition, medications such as corticosteroids and cytotoxic agents, and viral infections, can also contribute to a reduction in lymphocyte count. Despite these limitations, the SLICC committee recommends no change in the elements of the hematologic criterion when this criterion is properly interpreted and other causes of cytopenia are excluded.

Anemia, Hemolytic↗
PubMed2001

Association of osteoporosis and cardiovascular disease in women with systemic lupus erythematosus.

OBJECTIVE: Young women with lupus are at increased risk for premature osteoporosis and cardiovascular disease. Experimental evidence suggests that inflammation and immune-mediated mechanisms, key factors in the pathogenesis of lupus, play a role in osteogenesis and atherogenesis. This study investigated whether bone mineral density (BMD) was associated with the carotid plaque index, intima media thickness (IMT), or coronary artery calcium score in lupus patients. METHODS: In this pilot study, 65 women with lupus underwent carotid B-mode ultrasound to measure the carotid plaque index and IMT, and dual x-ray absorptiometry to measure BMD at the lumbar spine and hip. As part of a feasibility study, 13 of these 65 patients also underwent electron-beam computed tomography to assess coronary artery calcification. RESULTS: The carotid plaque index was higher (1.00, 1.00, and 0.38, respectively) in the patients in the lowest and middle tertiles of hip BMD when compared with patients in the highest tertile of hip BMD. The correlation coefficient between the coronary artery calcium score and lumbar spine BMD was -0.57 (P = 0.04), and between the coronary artery calcium score and hip BMD was -0.55 (P = 0.05). CONCLUSION: These results demonstrate an association between decreased BMD and both an increased carotid plaque index and presence of coronary artery calcification in a small cohort of young women with lupus.

Adult↗
PubMed2001

Vascular stiffness in women with systemic lupus erythematosus.

Large-vessel manifestations of systemic lupus erythematosus (SLE), a multisystem disease characterized by disturbances in the immune system, include higher than expected rates of hypertension and cardiovascular disease. Reductions in the elasticity of central arteries may act as a marker of early changes that predispose to the development of major vascular disease. This study evaluated risk factors associated with aortic stiffness measured by pulse wave velocity (PWV) in women with SLE. We expected SLE-specific factors, especially variables indicative of inflammation and active disease, to be associated with increasing PWV. The study population included 220 women currently enrolled in the Pittsburgh Lupus REGISTRY: All risk factor data were collected on the day of the ultrasound examinations. PWV waveforms were collected from the right carotid and femoral arteries by Doppler probes. The mean age of the women was 45.5+/-10.8 years, the median SLE disease duration approximated 9 years, and the mean PWV was 6.1+/-1.7 m/s. Multiple regression models were stratified by menopausal status. Among postmenopausal women, PWV risk factors were primarily traditional factors and included age, systolic blood pressure, family history of vascular disease, carotid plaque, creatinine, obesity, glucose, white cell count, and cumulative SLE organ damage. Among premenopausal women, PWV risk factors consisted of a mix of SLE-related and traditional variables and included higher C3 levels, presence of ds-DNA antibodies, nonuse of hydroxychloroquine, lower leukocyte count, higher mean arterial pressure, and carotid plaque. SLE-specific variables appeared to be associated with increases in aortic PWV, indicating central artery stiffening. This was seen most clearly among premenopausal women. This finding may partially explain the higher rates of cardiovascular disease and hypertension observed in young women with SLE.

Adult↗
PubMed2001

Epidemiology of systemic lupus erythematosus.

Tracking the epidemiology of systemic lupus erythematosus is problematic because the diagnosis can be elusive. Systematic review of cases is also difficult because of the varying paths these patients take through the medical provider system. In general, 7 women are stricken with the disease for every man, with an 11:1 female-to-male ratio during the childbearing years. African-Americans are disproportionately afflicted, and evidence is at least suggesting a higher prevalence among other ethnic groups including Hispanics, Asians, and native Americans. Difficulties with defining the patient population, along with minimal education for physicians, may contribute to suboptimal treatment, especially in the critical early stages of disease.

Diagnosis, Differential↗