Cancer risk in systemic lupus: an updated international multi-centre cohort study.

OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). CONCLUSION: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.

Stability of hematologic analytes in monkey, rabbit, rat, and mouse blood stored at 4°C in EDTA using the ADVIA 120 hematology analyzer.

BACKGROUND: The time from sampling to analysis can be delayed when blood samples are shipped to distant reference laboratories or when analysis cannot be readily performed. OBJECTIVE: The objective of this study was to evaluate the stability of hematologic analytes in blood samples from monkeys, rabbits, rats, and mice when samples were stored for up to 72 hours at 4°C. METHODS: Blood samples from 30 monkeys, 15 rabbits, 20 rats, and 30 mice were collected into EDTA-containing tubes and were initially analyzed within 1 hour of collection using the ADVIA 120 analyzer. The samples were then stored at 4°C and reanalyzed at 24, 48, and 72 hours after collection. RESULTS: Significant (P<.0003) changes in hematologic analytes and calculations included increased HCT and MCV and decreased MCHC and cell hemoglobin concentration mean (CHCM) at 72 hours and increased MPV at 24 hours in monkeys; increased MCV at 72 hours and MPV at 48 hours and decreased monocyte count at 24 hours in rabbits; increased MCV and decreased MCHC, CHCM, and monocyte count at 24 hours in rats; increased MCV, red cell distribution width, and MPV and decreased MCHC, CHCM, and monocyte count at 24 hours in mice. CONCLUSIONS: Although most of the changes in the hematologic analytes in blood from monkeys, rabbits, rats, and mice when samples were stored at 4°C were analytically acceptable and clinically negligible, the best practice in measuring hematologic analytes in these animals is timely processing of blood samples, preferably within 1 hour after collection.

Comparison of the vanadate oxidase method with the diazo method for serum bilirubin determination in dog, monkey, and rat.

The most widely used method for bilirubin concentration determination is the diazo method, which measures the color of azobilirubin. The vanadate oxidase method is based on oxidation of bilirubin to biliverdin by vanadate. The objective of this study was to compare total and direct bilirubin concentration ([Bt] and [Bd], respectively) determined by the diazo and vanadate oxidase methods in pooled serum samples from dogs, monkeys, and rats spiked with panels of different concentrations of bilirubin standards. Pooled serum samples from 40 dogs, 40 monkeys, and 60 rats were spiked with either ditaurine conjugates of bilirubin or a standard reference material. The results obtained from both assays were compared using Deming regression analysis. The intra- and interassay precision, expressed as a percentage of the coefficient of variation (%CV), was determined for [Bt] and [Bd], and the mean percentage of recovery was calculated. The vanadate oxidase method displayed an excellent correlation (r  =  0.99-1.00) with the diazo method. Using Deming regression, there were minimal negative or positive constant and proportional biases for [Bt] and [Bd]. The precision studies revealed that the vanadate oxidase method has comparable between-run and within-run CVs to those of the diazo method. The recovery study demonstrated that the diazo method more closely approximates the expected values of [Bt]. In conclusion, the vanadate oxidase method is a simple and rapid method that can be employed as an alternative to the diazo method when interfering substances are present in the serum samples of dog, monkey, and rat.

Determination of plasma fibrinogen concentrations in beagle dogs, cynomolgus monkeys, New Zealand white rabbits, and Sprague-Dawley rats by using Clauss and prothrombin-time-derived assays.

The most widely used technique for determination of fibrinogen concentration is the Clauss fibrinogen (FIB(Clauss)) assay, which measures the clotting time of plasma after addition of excess thrombin. More recently, the PT-derived fibrinogen (FIB(PT)) assay has been developed, based on the relationship between fibrinogen concentration and the kinetics of clot formation during the prothrombin time. The objective of this study was to compare the fibrinogen concentration determined by the FIB(Clauss) and FIB(PT) assays in citrated plasma samples from healthy dogs (n = 40), monkeys (n = 40), rabbits (n = 26), and rats (n = 58) by using an automated coagulation analyzer. Results of a t test analysis indicated that the mean plasma fibrinogen concentrations measured by the 2 assays for all 4 species were significantly different. According to Pearson correlation coefficients, the FIB(PT) assay displayed a high correlation (0.93 to 0.98) with the FIB(Clauss) assay for all species. When the FIB(PT) and FIB(Clauss) assays were compared by using Deming regression, positive or negative constant and proportional biases emerged for all species. Intra- and interassay coefficients of variation for the FIB(PT) and FI(BClauss) assays were 0.8% to 2.3% and 1.8% to 7.4%, respectively. In conclusion, the FIB(PT) assay is a rapid and economical method for estimating fibrinogen concentration in plasma samples from dogs, monkeys, rabbits, and rats. However, it should not be used without restriction. Further studies are required to investigate the performance of this assay in animals with various pathologic states, including coagulopathy, dysfibrinogenemia, and hypo- or hyperfibrinogenemia.

Treatments for carpal tunnel syndrome: who does what, when ... and why?

OBJECTIVE: To determine how frequently treatments had been offered to patients with suspected diagnoses of carpal tunnel syndrome (CTS) who had been referred for confirmatory nerve conduction studies (NCSs) and to identify potential predictors of such treatment. A follow-up survey was conducted to determine the effect of NCS results on subsequent treatment. DESIGN: Self-administered survey questionnaire and follow-up telephone survey. SETTING: Royal University Hospital at the University of Saskatchewan in Saskatoon. PARTICIPANTS: Two hundred eleven patients with clinically suspected CTS who had been referred for confirmatory NCS. MAIN OUTCOME MEASURES: Results of NCSs, number of patients prescribed wrist splints or nonsteroidal anti-inflammatory drugs (NSAIDs) before and after NCSs, patient characteristics associated with being prescribed therapy, and reporting benefit of therapy. RESULTS: Nerve conduction studies confirmed CTS in 121 (57.3%) of the 211 study patients. Before NCSs, wrist splints and NSAIDs had been prescribed to 33.2% and 38.8% of patients, respectively. Splints and NSAIDs were reported to alleviate symptoms by 78.3% and 74% of patients, respectively, who received such treatments. No significant differences in age, sex, body mass index, symptom duration, symptom or function scores, or subsequent NCS results were noted between patients who were and were not prescribed these therapies or between those who did or did not report improvement in symptoms. Results of the follow-up survey indicated that the number of recommendations for splints and NSAIDs had doubled after NCSs were completed and that surgical intervention had been at least discussed in most cases. Treatment recommendations, including surgery, however, were not associated with identifiable patient factors, including patients' NCS results. CONCLUSION: Some patients were prescribed conservative treatments before NCSs. Following NCSs, prescriptions for wrist splints or NSAIDs approximately doubled. Interestingly, NCS results did not appear to influence subsequent therapeutic decision-making for either conservative treatment or surgical options. We think these findings suggest a lack of confidence in electrodiagnostic study results. It would be interesting to evaluate a larger population of primary care patients prospectively to examine further the use of NCSs in current clinical decision-making.

Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis.

BACKGROUND: Several clinical and experimental lines of evidence suggest that leucotriene B4 (LTB4), an arachidonic acid derivative with potent proinflammatory properties, plays a key role in the pathophysiology of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the efficacy and safety of BIIL 284, an oral long-acting LTB4 receptor antagonist, as monotherapy for the treatment of patients with active RA. METHODS: This was a multi-centre, randomised, double-blind, placebo-controlled trial of patients with active RA of 3 months' duration. A total of 342 patients were randomised to receive 5 mg, 25 mg or 75 mg of BIIL 284 or placebo. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR) 20. RESULTS: Although a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg and 75 mg of BIIL 284 compared with those treated with placebo, no statistically significant differences were found between any of the three active treatment groups compared with the placebo group with regard to the primary or secondary end points. All trial treatments were safe and well tolerated. CONCLUSIONS: This clinical trial demonstrates that treatment of patients with active RA with a potent oral long-acting LTB4 receptor antagonist produced only modest improvements in disease activity. The results of this trial support the conclusion that LTB4 is not a major contributor to the inflammatory process in RA.

Designing a biocontainment unit to care for patients with serious communicable diseases: a consensus statement.

In spite of great advances in medicine, serious communicable diseases are a significant threat. Hospitals must be prepared to deal with patients who are infected with pathogens introduced by a bioterrorist act (e.g., smallpox), by a global emerging infectious disease (e.g., avian influenza, viral hemorrhagic fevers), or by a laboratory accident. One approach to hazardous infectious diseases in the hospital setting is a biocontainment patient care unit (BPCU). This article represents the consensus recommendations from a conference of civilian and military professionals involved in the various aspects of BPCUs. The role of these units in overall U.S. preparedness efforts is discussed. Technical issues, including medical care issues (e.g., diagnostic services, unit access); infection control issues (e.g., disinfection, personal protective equipment); facility design, structure, and construction features; and psychosocial and ethical issues, are summarized and addressed in detail in an appendix. The consensus recommendations are presented to standardize the planning, design, construction, and operation of BPCUs as one element of the U.S. preparedness effort.

Sparing of age-related macular degeneration in rheumatoid arthritis.

Age-related macular degeneration (AMD), for which inflammatory changes have been demonstrated, is the commonest cause of blindness in the elderly. We compared the prevalence of AMD in a prospectively followed cohort of rheumatoid arthritic (RA) patients from Saskatchewan with published data from four racially similar general populations. For individuals 65 years or older, only three cases of AMD were identified in the Saskatchewan cohort of 993 RA patients (0.2% prevalence). This compares with 67 out of 1955 subjects in the Beaver Dam survey (prevalence 3.43%); 101 out of 4071 in the Rotterdam survey (prevalence 2.48%); and 63 out of 1950 in the Blue Mountains survey (prevalence 3.23%). For individuals 75 years or older, only two cases out of 497 were identified in the RA cohort (prevalence 0.40%), compared with 516 cases out of 13,900 in the United Kingdom survey (prevalence 3.72%). Patients with RA appear to be relatively spared from AMD. We hypothesize that this results from long term antiinflammatory treatment. Genetic or environmental factors could also be responsible.

Rheumatologists' adherence to guidelines for misoprostol use in patients at high risk for nonsteroidal antiinflammatory drug gastropathy.

OBJECTIVE: To determine the extent of evidence based practice among rheumatologists in the prevention of nonsteroidal antiinflammatory drug (NSAID) associated peptic ulcer disease and to seek ways to improve the management of high risk NSAID users. METHODS: In March 1996 all 7 rheumatologists from Saskatoon participated in a consensus conference to develop local guidelines for the prophylaxis of NSAID associated peptic ulcer disease. We performed a retrospective chart review for September/October 1995 (baseline) and for June/July 1996 (post-consensus guideline) of all patients from Saskatoon rheumatologists who were being treated with NSAID for either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis (IP). A prospective crossover intervention study was performed from January to April 1997 in which 2 subgroups of rheumatologists (university or private practice) had a reminder sheet of gastrointestinal (GI) bleeding risk assessment placed into the front of each patient's chart prior to each office visit. The GI bleeding risk for each patient at time of visit was later determined by chart review. The primary outcome was the proportion of adherence to guidelines for high risk NSAID users in the combined intervention group (reminder sheet) compared to the combined control group (no reminder sheet) in the prospective controlled crossover study. RESULTS: A total of 484 patients with RA or IP received NSAID during the 4 study periods. Of these, 82 patients (16.9%) were at high risk of GI bleed. In 1995, the proportion of high risk patients taking misoprostol was 29% for university and 33% for private practice rheumatologists. The establishment of local consensus guidelines in 1996 temporarily increased adherence to guidelines to 43%, but only for private practice rheumatologists. During the prospective study, adherence to guidelines was significantly greater in the intervention (reminder sheets) group compared to the control (no reminder sheets) group (53% vs 15%; p = 0.014). CONCLUSION: The simple intervention of reminder sheets for GI bleeding risk assessment resulted in a significant increase in rheumatologists' adherence to guidelines, although a substantial number of patients remained untreated with misoprostol. This study illustrates the difficulty of incorporating new knowledge and recommendations into clinical practice. Additional strategies should be investigated to more effectively incorporate new knowledge in the practice of rheumatology.