Biomedical subjects
Publications and source records attributed to M Petri.
The Hopkins Lupus Cohort is a decade-long prospective study, now numbering 800 patients with systemic lupus erythematosus. In this article, predictors of disease activity, disease damage (including accelerated atherosclerosis and antiphospholipid antibody syndrome) and health status are reviewed.
Many institutions worldwide are conducting clinical studies using immunoablative therapy followed by hematopoietic stem cell transplantation for the treatment of SLE. Interpretation of these studies will be complicated by the differences in patient selection, conditioning regimens, and the method of stem cell collection. A major concern with this approach is that autoreactive effector cells will be re-infused with the autologous graft. The recent demonstration that immunoablative therapy (cyclophosphamide 200 mg/kg) can be safely delivered without the need for stem cell rescue offers a potential way to circumvent this problem. Early results employing immunoablative therapy, with or without stem cell rescue, are encouraging; however, longer follow-up and additional patients are necessary to validate this approach.
Studies of cognitive functioning in patients with systemic lupus erythematosus (SLE) have found deficits even in patients without other evidence of neurologic involvement. The present study used scores on the 11 items of the Mini-Mental State Exam (MMSE) to classify the cognitive impairment of 93 SLE patients as suggestive of "cortical" or "subcortical" dysfunction using a validated statistical algorithm. Ninety-five percent of patients were categorized as having "subcortical" deficits, and 5% were categorized as having "cortical" deficits. When the analysis was limited to only those with total MMSE scores < or = 24, 81% were classified as "subcortical" and 19% as "cortical." These results suggest that SLE patients can have psychomotor and mental tracking deficits of a type seen in patients with subcortical brain disease, even in the absence of gross neurologic involvement.
Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
The goal of the 'Outcome Measures in Rheumatology' (OMERACT) process is to select domains and/or outcome measures for clinical trials in each defined disease category according to truth, discrimination and feasibility. OMERACT IV, held in Cancun, Mexico, April 1998, included the module 'Systemic Lupus Erythematosus (SLE)', designed to define a preliminary core set of outcome domains for randomized controlled trials and longitudinal observational studies (LOS). Although specific measures to be used in clinical trials of SLE have yet to be determined, both randomized controlled trials and longitudinal observation studies groups recommended that outcome be assessed in terms of disease activity and damage in all organ systems involved, as well as by health related quality of life, meaningful to patients, and adverse events. These recommendations were ratified by the majority of participants. In a heterogeneous patient population such as SLE, it is recognized that any individual measure of clinical response may reflect only a portion of what might be termed the 'true outcome'. A responder index could integrate such relatively independent measures of outcome into a single assessment, potentially increasing statistical power and decreasing sample size. Results from randomized controlled trials currently underway assessing these outcome domains are eagerly awaited, and are expected to rapidly advance the field.
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OBJECTIVE: To compare patients with systemic lupus erythematosus (SLE) from different centers with respect to demographics and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and to assess whether the SLICC/ACR DI changed over time, and whether initial DI scores were related to outcome. METHODS: Members of SLICC completed DI scores and patient demographics on patients followed in their centers. Information was provided at 2, 5-10, and > 10 years of followup. Data were entered on computer and analyzed on SPSS/PC+ and SAS using descriptive statistics and analysis of variance. RESULTS: Information for 1297 patients within 2 years of first clinic visit was submitted from 8 centers. There were 1187 women and 110 men with a mean age at diagnosis of SLE of 32 years. Seven hundred sixty-two were Caucasian, 423 were black, and the remainder were of other races. There were more blacks in the American centers than in Canadian or European centers. Five centers provided information for the 3 time periods. The DI increased over time. Ninety-nine patients had died. Higher SLICC/ACR DI scores were documented in patients who went on to die. CONCLUSION: The SLICC/ACR DI is a valid measure for damage in SLE.
OBJECTIVE: To determine the association between fibromyalgia (FM) tender points (TP) and psychological constructs in patients with systemic lupus erythematosus (SLE). METHODS: One hundred seventy-three patients with SLE were examined for FM TP, and asked to complete 2 questionnaires at the same visit, the Health-Related Hardiness Scale (HRHS), and the Mishel Uncertainty in Illness Scale (MUIS). RESULTS: The examination of FM TP showed that 38.2% had no TP, 44.5% had 1-10 TP, and 17.3% had > or = 11 TP. The mean +/- SD score of the HRHS was 155.6 +/- 19.7 (range 105.0-198.0; higher scores indicate greater hardiness), and the MUIS was 85.3 +/- 18.7 (range 41.0-132.0; higher scores indicate uncertainty). There were significant associations between FM TP and HRHS (no TP 161.2 +/- 20.2, 1-10 TP 152.5 +/- 19.7, > or = 11 TP 151.0 +/- 15.8; p = 0.0108) and between FM TP and MUIS (no TP 78.2 +/- 20.2, 1-10 TP 86.9 +/- 17.6, > or = 11 TP 95.8 +/- 14.7; p = 0.0001). CONCLUSION: This study shows a strong association between FM TP and uncertainty or lack of "hardiness." We conclude that SLE patients with FM TP are less likely to be good "copers." Prospective studies to determine if "poor coping" predicts FM in SLE are recommended. If the association between coping and FM is causal, it will justify interventions to improve coping and similar constructs, such as self-efficacy.
OBJECTIVE: Patients with systemic lupus erythematosus (SLE) in USA increasingly have their care centered in health maintenance organizations (HMO). We examined whether HMO and non-HMO SLE patients with renal involvement, who had the same university rheumatologist, differed in their utilization of health care or renal outcomes. METHODS: Consecutive patients with SLE with renal involvement (n = 24), 10 enrolled in an HMO, 14 not, were studied. Laboratory values were prospectively determined. RESULTS: At the first visit to the rheumatologist, there was no significant difference between HMO and non-HMO patients in laboratory values. There was no difference in the 2 groups in the final prednisone dose (HMO 12 mg vs non-HMO 15.9 mg) or use of azathioprine (20% vs. 57%; p = 0.07) or cyclophosphamide (60% vs. 57%). The serum creatinine was higher in the HMO patients (HMO 1.1 mg/dl vs. non-HMO 0.78 mg/dl; p = 0.05). No difference was found in the number of rheumatology visits. There was a significant difference in the number of communications from the rheumatologist to the HMO versus the HMO to the rheumatologist (p = 0.026). CONCLUSION: Other than the serum creatinine, there are no differences in the treatment or renal outcomes for HMO compared to non-HMO patients with SLE seeing the same rheumatologist. There is a potential barrier in physician communication, however, with the majority of communications going from the rheumatologist to the HMO provider.
OBJECTIVE: To define the epidemiology, clinical and radiographic presentation, treatment, and prognosis of atraumatic osteonecrosis of the humeral head. METHODS: Of the 1,056 patients managed for osteonecrosis of any joint between July 1, 1974, and December 1, 1996, 127 shoulders in 73 patients were treated for atraumatic osteonecrosis of the proximal humerus. Clinical and radiographic characterization of this patient cohort was performed. RESULTS: At presentation, there were 47 women and 26 men with a mean age of 41 years (range 20-60). Numerous associated factors were noted: alcohol use (38%), moderate smoking (30%), asthma (8%), and nephrosis (3%). A corticosteroid association was noted in 60 patients (82%) and 42 of the patients (58%) had an immunocompromising disease. The severity of humeral head osteonecrosis did not correlate with dose or duration of corticosteroid therapy. According to the modified Ficat and Arlet radiographic staging system, there were 20 shoulders with Stage I disease, 55 shoulders with stage II disease, and 52 shoulders with Stage ITI or IV disease. Seventy-four of the shoulders treated with core decompression (78%) had good to excellent clinical outcomes at a mean followup of 6 years (range 2-21). Fourteen of the 16 patients (88%) treated with hemiarthroplasty or total shoulder arthroplasty were clinically successful at a mean followup 4 years (range 2-11). CONCLUSION: We observed a low incidence of humeral head involvement in the osteonecrosis patient cohort (7% of all osteonecrosis patients), and a high incidence of corticosteroid use (82%). hip involvement (81%), and bilateral disease (74%). Osteonecrosis of the humeral head should be suspected in patients presenting with shoulder pain and a history of osteonecrosis in other joints. Hip screening for osteonecrosis is advocated in patients with shoulder involvement. Early detection of shoulder osteonecrosis may permit a more conservative, joint-sparing approach as an alternative to surgical management.
OBJECTIVE: Tissue factor (TF) is the major intrinsic initiator of clotting. TF expression on monocytes has been associated with high titers of anticardiolipin antibodies (aCL) in patients with antiphospholipid syndrome (APS) with thrombosis. We investigated the influence of clinical factors on TF activity in blood from patients with systemic lupus erythematosus (SLE) and examined the relationship between aCL and TF. METHODS: In this cross sectional study, consecutive patients with SLE from one rheumatology clinic gave blood samples for measurement of TF activity, aCL, and Russell viper venom time. We assessed disease activity by measuring sedimentation rate, anti-dsDNA, and complement components C3 and C4, and measured clinical indices. Associations were investigated with the Wilcoxon rank-sum test and linear regression. RESULTS: Sixty-nine patients contributed blood samples. The median age was 38 years, and 10 of the SLE patients had a history of thrombosis. Patients with active arthritis had TF activity 1.3 times that in patients without arthritis (p = 0.028). Users of nonsteroidal antiinflammatory drugs (NSAID) had TF activity significantly lower than nonusers (p = 0.010). Patients with previous thrombosis had TF activity significantly lower than patients without thrombosis (p < 0.001). Overall, aCL and TF activity were not associated when we adjusted for these clinical factors. CONCLUSION: Arthritis, previous thrombosis, and use of NSAID significantly modified TF activity in patients with SLE. Unlike previous reports, we found no association between aCL titer and TF activity, which may be due to our adjusting for other important clinical factors.
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The authors expound the case of a 47 years old woman who was operated on 25 months ago for bowels necrosis caused from occlusion of arteria mesenterica superior. The operation was composed of a partial jejunale resection, total ileum resection and a right side hemicolectomy, the residual part of the intestine (jejunum) is 70-80 cm. Eleven months after the operation her status has got worse with 10-12 watery faeceses, abdominal pain and body weight losing (15 kg in 2 months). In the beginning a complete central parenteral and enteral nutrition was necessary. The authors expound the complications connected with the nutrition and the successful rehabilitation of the patient as well. They built her nutrition gradually completed with oral given nutriment. The nutritional status of the patient now is adequate and she is able to do the housekeeping.
OBJECTIVE: To describe patterns of systemic lupus (SLE) disease activity over time. METHODS: Disease activity was measured in a prospective cohort of 204 consecutive SLE patients followed up quarterly for 2.0-7.5 years (911 person-years of followup). Physician's global assessment (PGA) and modified SLE Disease Activity Index (M-SLEDAI; omitting serology) scores were plotted against time for each patient. Definitions for disease activity patterns were developed by consensus using these plots, and the proportion of total follow-up time represented by each pattern was calculated. RESULTS: Three patterns of SLE activity were apparent: relapsing-remitting (RR), chronic active (CA), and long quiescent (LQ). The CA pattern was the most frequent for both the PGA and M-SLEDAI, representing 58% and 40% of total person-years, respectively. The least common pattern was LQ (PGA 16%, M-SLEDAI 25%), while the RR pattern was intermediate in frequency (PGA 26%, M-SLEDAI 35%). Average disease activity during RR periods tended to be mild, while that during CA periods was more likely to be moderately severe. The most common discrepancy between instruments was that the PGA depicted CA when the M-SLEDAI showed an RR pattern. The M-SLEDAI did not appear to capture mild degrees of activity. CONCLUSION: SLE activity was readily classified into 1 of 3 patterns: RR, CA, or LQ. The CA pattern was most common, suggesting that significant morbidity may arise from persistent disease activity. These findings may have important implications regarding the choice of outcome measures in SLE clinical trials, since comparison of flare rates may not account for chronic disease activity.
Symptoms reliably attributable to menopause are vasomotor symptoms and vaginal dryness. Other symptoms are not directly related to the menopause. HRT or ERT are effective in providing symptom relief and preventing disease prevalent in postmenopausal women. HRT or ERT is beneficial in women with RA. Little data concerns safety in SLE patients, but there are theoretical advantages to using HRT or ERT in women with SLE and two studies that indicate it is safe. Other forms of treatment are available to women who cannot or will not use HRT or ERT.
Renal insufficiency is one of the most severe outcomes of systemic lupus erythematosus (SLE). The aim of this study was to identify baseline predictors of the development of renal insufficiency in a cohort of patients with SLE. 281 patients from the The Hopkins Lupus Cohort (HLC) enrolled between 1987-1994 were followed for the occurrence of renal insufficiency, defined as a serum creatinine 1.6 mg/dl for men and 1.4 mg/dl for women. Over a mean (+/-s.d.) of 3. 3+/-2.1 y of follow up, 46 (16%) of the 281 patients developed renal insufficiency. Using a multivariate Cox proportional hazard model, we found the risk of renal insufficiency associated with younger (0-19 y) or older (40 y) age at baseline (relative risk (95% CI) 5.1 (1.4, 18.8) and 4.1 (2.1, 8.2)) and longer duration of SLE before referral to the cohort (RR 1.25 [1.05, 1.5] for every five years). Additional predictive variables were borderline elevation of serum creatinine at baseline (RR 3.1 (1.4, 6.6) for a serum creatinine 1. 4-1.5 mg/dl for men and 1.2-1.3 mg/dl for women), and mean proteinuria (RR 3.6 (1.8, 7.4) for trace-3+ and 10.6 (3.8, 30.0) for 3+ (urine dipstick level)). Socioeconomic status, race, autoantibodies and complement were not significantly associated with the risk of renal insufficiency. This study supports early referral of SLE patients to rheumatologists and emphasizes the importance of early signs of renal involvement as predictors of later renal insufficiency in SLE patients.
Multiple reliable and valid disease activities indices exist and have been used successfully in longitudinal studies. However, the definition of flare, using these intruments, has not been universally decided or accepted. Because flare is one of the three major patterns of lupus activity, it will remain an important outcome measure in both longitudinal and clinical trial studies.
In contrast to the objective of most clinical trials, which is to demonstrate superiority of an experimental treatment over a standard or placebo, the aim of an equivalence trial is to show that two treatments are equivalent in outcome or only marginally different. This would be of interest when an experimental treatment offers advantages such as reduced toxicity, ease of administration, or cost relative to the standard. Demonstrating equivalence may also be a goal when evaluating the safety of certain drugs because similarity in the risks of an adverse event in subjects exposed and unexposed to the drug is an indication of its safety. The classical formulation of the null hypothesis of treatment equality that is used in superiority trials is not applicable to equivalence trials because absolute equivalence between treatment groups cannot be proven. The strategy in equivalence trials is to define a maximum difference between treatment groups that is clinically acceptable and then assess whether there is sufficient evidence from the trial to conclude that the true treatment difference is within this acceptable range. In this paper, we discuss issues surrounding the planning, conduct, and analysis of equivalence trials in the context of SLE, with examples from the SELENA study.