Tunable Photon Statistics Exploiting the Fano Effect in a Waveguide.

A strong optical nonlinearity arises when coherent light is scattered by a semiconductor quantum dot coupled to a nanophotonic waveguide. We exploit the Fano effect in such a waveguide to control the phase of the quantum interference underpinning the nonlinearity, experimentally demonstrating a tunable quantum optical filter which converts a coherent input state into either a bunched or an antibunched nonclassical output state. We show theoretically that the generation of nonclassical light is predicated on the formation of a two-photon bound state due to the interaction of the input coherent state with the quantum dot. Our model demonstrates that the tunable photon statistics arise from the dependence of the sign of two-photon interference (either constructive or destructive) on the detuning of the input relative to the Fano resonance.

Heap leach cyanide irrigation and risk to wildlife: Ramifications for the international cyanide management code.

Exposed cyanide-bearing solutions associated with gold and silver recovery processes in the mining industry pose a risk to wildlife that interact with these solutions. This has been documented with cyanide-bearing tailings storage facilities, however risks associated with heap leach facilities are poorly documented, monitored and audited. Gold and silver leaching heap leach facilities use cyanide, pH-stabilised, at concentrations deemed toxic to wildlife. Their design and management are known to result in exposed cyanide-bearing solutions that are accessible to and present a risk to wildlife. Monitoring of the presence of exposed solutions, wildlife interaction, interpretation of risks and associated wildlife deaths are poorly documented. This paper provides a list of critical monitoring criteria and attempts to predict wildlife guilds most at risk. Understanding the significance of risks to wildlife from exposed cyanide solutions is complex, involving seasonality, relative position of ponding, temporal nature of ponding, solution palatability, environmental conditions, in situ wildlife species inventory and provision of alternative drinking sources for wildlife. Although a number of heap leach operations are certified as complaint with the International Cyanide Management Code (Cyanide Code), these criteria are not considered by auditors nor has systematic monitoring regime data been published. Without systematic monitoring and further knowledge, wildlife deaths on heap leach facilities are likely to remain largely unrecorded. This has ramifications for those operations certified as compliance with the Cyanide Code.

Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist.

In the accompanying paper we describe how MRK-409 unexpectedly produced sedation in man at relatively low levels of GABA(A) receptor occupancy (∼10%). Since it was not clear whether this sedation was mediated via the α2/α3 or α1 GABA(A) subtype(s), we characterized the properties of TPA023B, a high-affinity imidazotriazine which, like MRK-409, has partial agonist efficacy at the α2 and α3 subtype but is an antagonist at the α1 subtype, at which MRK-409 has weak partial agonism. TPA023B gave dose- and time-dependent occupancy of rat brain GABA(A) receptors as measured using an in vivo [(3)H]flumazenil binding assay, with 50% occupancy corresponding to a respective dose and plasma drug concentration of 0.09 mg/kg and 19 ng/mL, the latter of which was similar to that observed in mice (25 ng/mL) and comparable to values obtained in baboon and man using [(11)C]flumazenil PET (10 and 5.8 ng/mL, respectively). TPA023B was anxiolytic in rodent and primate (squirrel monkey) models of anxiety (elevated plus maze, fear-potentiated startle, conditioned suppression of drinking, conditioned emotional response) yet had no significant effects in rodent or primate assays of ataxia and/or myorelaxation (rotarod, chain-pulling, lever pressing), up to doses (10 mg/kg) corresponding to occupancy of greater than 99%. In man, TPA023B was well tolerated at a dose (1.5 mg) that produced occupancy of >50%, suggesting that the sedation previously seen with MRK-409 is due to the partial agonist efficacy of that compound at the α1 subtype, and highlighting the importance of antagonist efficacy at this particular GABA(A) receptor population for avoiding sedation in man.

Use of intravenous immune globulin in the ICU: a retrospective review of prescribing practices and patient outcomes.

RATIONALE: Intravenous immune globulin (IVIG) is a pooled human blood product. Much of IVIG use in Canada is prescribed for 'unlabelled' or 'off-label' indications. Due to costs, risk of use and limited supply, knowledge about the use of IVIG is important. We collected data regarding the usage of IVIG and outcomes of patients receiving IVIG in the intensive care units (ICUs) of two community and three academic hospitals. METHODS: We reviewed the charts of adult patients who received IVIG in the five ICUs over a 5-year period. Data collection included demographics, severity of illness, indication for and dose of IVIG, mortality and adverse effects. On the basis of a classification developed by Canadian Blood Services, the indications for IVIG were then classified as 'appropriate' or 'inappropriate'. RESULTS: One hundred and forty-five patients received IVIG in the ICU. In all, 19% of IVIG prescriptions were for 'appropriate' indications and 7% were 'inappropriate'. The remaining 74% were prescribed for indications with some evidence to support their use. Three indications accounted for 50% of all IVIG prescribed: Guillain-Barre syndrome (GBS), necrotising fasciitis (NF) and toxic epidermal necrolysis (TEN). Both the community and academic centres prescribed IVIG for similar indications. Adverse effects associated with IVIG administration included deep vein thrombosis/pulmonary embolism, fever and renal failure, although direct causation related to IVIG could not be established. The overall mortality rate was 55%. CONCLUSIONS: IVIG is used relatively infrequently in the critical care setting. The most common indications were GBS, TEN and NF. Mortality was high. There was no difference between community and academic ICUs.

Predictors of mortality in patients undergoing autologous hematopoietic cell transplantation admitted to the intensive care unit.

Between January 2001 and July 2006, 1013 patients received autologous hematopoietic cell transplants (AHCT) at Canada's largest transplant center. In this retrospective cohort study of AHCT patients admitted to the intensive care unit (ICU), we describe the outcomes following ICU admission and the variables measured in the first 24 h of ICU admission associated with overall ICU mortality. Results indicate a 3.3% ICU admission rate (n=34) with 13 deaths (1% overall mortality rate, 38% in ICU mortality rate). The worst outcome was in AL amyloid patients of whom 28% were admitted to the ICU, with an ICU mortality rate of 55%. The Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) score in the first 24 h were statistically associated with mortality by univariate analysis. Other variables measured at 24 h and associated with ICU mortality included multiorgan failure, mechanical ventilation, inotropic support >4 h and Gram-negative sepsis. Our data indicate that ICU admission in the autotransplant population is rare and that it is influenced by underlying diagnosis, with AL amyloid patients having the highest risk. Our observations may assist clinical decision-making regarding the continuation of intensive care delivered 24 h after ICU admission.

Practising evidence-based medicine: the design and implementation of a multidisciplinary team-driven extubation protocol.

BACKGROUND: Evidence from recent literature shows that protocol-directed extubation is a useful approach to liberate patients from mechanical ventilation (MV). However, research evidence does not necessarily provide guidance on how to implement changes in individual intensive care units (ICUs). We conducted the present study to determine whether such an evidence-based strategy can be implemented safely and effectively using a multidisciplinary team (MDT) approach. METHOD: We designed a MDT-driven extubation protocol. Multiple meetings were held to encourage constructive criticism of the design by attending physicians, nurses and respiratory care practitioners (RCPs), in order to define a protocol that was evidence based and acceptable to all clinical staff involved in the process of extubation. It was subsequently implemented and evaluated in our medical/ surgical ICU. Outcomes included response of the MDT to the initiative, duration of MV and stay in the ICU, as well as reintubation rate. RESULTS: The MDT responded favourably to the design and implementation of this MDT-driven extubation protocol, because it provided greater autonomy to the staff. Outcomes reported in the literature and in the historical control group were compared with those in the protocol group, and indicated similar durations of MV and ICU stay, as well as reintubation rates. No adverse events were documented. CONCLUSION: An MDT approach to protocol-directed extubation can be implemented safely and effectively in a multidisciplinary ICU. Such an effort is viewed favourably by the entire team and is useful in enhancing team building.

Patient handling of a dry-powder inhaler in clinical practice.

BACKGROUND: Multi-dose dry-powder inhalers are perceived as being easier for patients to use than conventional pressurized aerosol inhalers; however, no study has determined whether patients handle such devices adequately and whether there is a need for patient education in this area. METHOD: We used trained observers to assess the handling of a specific multi-dose dry powder inhaler (Turbuhaler; AstraZeneca Canada; Mississauga, ON) by patients currently using the device for the management of their asthma. Fourteen discrete steps were scored independently by two observers simultaneously. Patients were divided into two groups for analysis: those who had received formal instruction in the use of the inhaler at The Asthma Centre and those who had received no formal instruction in the community. RESULTS: There was no significant difference between the formally trained groups and control groups in the percentage of handling steps performed correctly (79% vs 78%, respectively; p > 0.05). Fewer than 50% of patients in both groups demonstrated optimal breath-holding when using the device. CONCLUSION: Patient handling of Turbuhaler was generally good, with no evidence that a structured education intervention offered an advantage over the usual education incidental to the prescribing or dispensing process. The most common handling flaw, suboptimal breath-holding, is not specific to this device and is of uncertain clinical significance.

Handheld computers in critical care.

BACKGROUND: Computing technology has the potential to improve health care management but is often underutilized. Handheld computers are versatile and relatively inexpensive, bringing the benefits of computers to the bedside. We evaluated the role of this technology for managing patient data and accessing medical reference information, in an academic intensive-care unit (ICU). METHODS: Palm III series handheld devices were given to the ICU team, each installed with medical reference information, schedules, and contact numbers. Users underwent a 1-hour training session introducing the hardware and software. Various patient data management applications were assessed during the study period. Qualitative assessment of the benefits, drawbacks, and suggestions was performed by an independent company, using focus groups. An objective comparison between a paper and electronic handheld textbook was achieved using clinical scenario tests. RESULTS: During the 6-month study period, the 20 physicians and 6 paramedical staff who used the handheld devices found them convenient and functional but suggested more comprehensive training and improved search facilities. Comparison of the handheld computer with the conventional paper text revealed equivalence. Access to computerized patient information improved communication, particularly with regard to long-stay patients, but changes to the software and the process were suggested. CONCLUSIONS: The introduction of this technology was well received despite differences in users' familiarity with the devices. Handheld computers have potential in the ICU, but systems need to be developed specifically for the critical-care environment.

Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and efficacy of high-frequency oscillatory ventilation (HFOV) in adult patients with the acute respiratory distress syndrome (ARDS) and oxygenation failure. DESIGN: Prospective, clinical study. SETTING: Intensive care and burn units of two university teaching hospitals. PATIENTS: Twenty-four adults (10 females, 14 males, aged 48.5 +/- 15.2 yrs, Acute Physiology and Chronic Health Evaluation II score 21.5 +/- 6.9) with ARDS (lung injury score 3.4 +/- 0.6, Pao2/Fio2 98.8 +/- 39.0 mm Hg, and oxygenation index 32.5 +/- 19.6) who met one of the following criteria: Pao2 < or =65 mm Hg with Fio2 > or =0.6, or plateau pressure > or =35 cm H2O. INTERVENTIONS: HFOV was initiated in patients with ARDS after varying periods of conventional ventilation (CV). Mean airway pressure (Paw) was initially set 5 cm H2O greater than Paw during CV, and was subsequently titrated to maintain oxygen saturation between 88% and 93% and Fio2 < or =0.60. MEASUREMENTS AND MAIN RESULTS: Fio2, Paw, pressure amplitude of oscillation, frequency, blood pressure, heart rate, and arterial blood gases were monitored during the transition from CV to HFOV, and every 8 hrs thereafter for 72 hrs. In 16 patients who had pulmonary artery catheters in place, cardiac hemodynamics were recorded at the same time intervals. Throughout the HFOV trial, Paw was significantly higher than that applied during CV. Within 8 hrs of HFOV application, and for the duration of the trial, Fio2 and Paco2 were lower, and Pao2/Fio2 was higher than baseline values during CV. Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure (at 8 and 40 hrs) and central venous pressure (at 16 and 40 hrs), and a reduction in cardiac output throughout the course of the study. There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV. Complications occurring during HFOV included pneumothorax in two patients and desiccation of secretions in one patient. Survival at 30 days was 33%, with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors (1.6 +/- 1.2 vs. 7.8 +/- 5.8 days; p =.001). CONCLUSIONS: These findings suggest that HFOV has beneficial effects on oxygenation and ventilation, and may be a safe and effective rescue therapy for patients with severe oxygenation failure. In addition, early institution of HFOV may be advantageous.

3-(4-Fluoropiperidin-3-yl)-2-phenylindoles as high affinity, selective, and orally bioavailable h5-HT(2A) receptor antagonists.

The development of very high affinity, selective, and bioavailable h5-HT(2A) receptor antagonists is described. By investigation of the optimal position for the basic nitrogen in a series of 2-phenyl-3-piperidylindoles, it was found that with the basic nitrogen at the 3-position of the piperidine it was not necessary to further substitute the piperidine in order to obtain good binding at h5-HT(2A) receptors. This meant the compounds no longer had high affinity at the IKr potassium channel, an issue with previous series of 2-aryl-3-(4-piperidyl)indoles. Improvements could be made to oral bioavailability in this series by reduction of the pK(a) of the basic nitrogen, by adding a fluorine atom to the piperidine ring, leading to 3-(4-fluoropiperidin-3-yl)-2-phenyl-1H-indole (17). Metabolic studies with this compound identified oxidation at the 6-position of the indole as a major route in vitro and in vivo in rats. Blocking this position with a fluorine atom led to 6-fluoro-3-(4-fluoropiperidin-3-yl)-2-phenyl-1H-indole (22), an antagonist with 0.06 nM affinity for h5-HT(2A) receptors, with bioavailability of 80% and half-life of 12 h in rats.

Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus.

The aim of this study was to determine whether early damage accrued in SLE as measured by the SLICC/ACR Damage Index predicts mortality in an inception cohort of lupus patients that have been followed prospectively in a single centre. SLE patients from the University of Toronto Lupus Clinic presenting within 1 y of their diagnosis prior to 1988 were included. This enabled all patients to be potentially followed for at least 10 y. Yearly SLICC/ACR Damage Index scores were determined for each patient. Early damage was defined as a score > or = 1 and no damage as a score of 0 at the initial assessment. Log rank test was used to compare the survival experience between those with and without damage, with all patients being censored at 10 y. Two-hundred and sixty-three patients were identified in this inception cohort who were followed for 10 y. One-hundred and ninety patients (72%) had a SLICC/ACR Damage Index score of 0 (no damage) while 73 patients (28%) had at least one SLICC/ACR Damage Index item scored (early damage). Twenty-five percent of lupus patients who exhibited damage at their first SLICC/ACR Damage Index assessment died within 10 y of their illness as compared to only 7.3% who had no early damage (log rank P-value = 0.0002). SLE patients who died within 10 y were more likely to have renal damage (P = 0.013), and a trend toward more cardiovascular disease (P = 0.056), compared to patients who were alive. Early damage as reflected by the initial SLICC/ACR Damage Index is associated with a higher rate of mortality.

Serial renal biopsy in systemic lupus erythematosus.

OBJECTIVE: To examine the role of sequential renal biopsies in patients with systemic lupus erythematosus (SLE), with regard to indications, morphologic change over time, and the clinical utility of repeat biopsies. METHODS: Patients with repeat renal biopsies were identified from the University of Toronto Lupus Clinic Database and their biopsies were reviewed blindly by a committee, using the WHO classification as well as activity and chronicity indices. Reasons for obtaining biopsy were documented, and therapeutic decisions following repeat biopsy were tabulated. RESULTS: Fifty-seven patients (49 F/9 M) had at least 2 renal biopsies between 1970 and 1994. The mean interval between biopsies was 4.2 years. The major reason for obtaining the first biopsy was disease diagnosis (32/57), while the majority of repeat biopsies were performed to discern the cause of increasing proteinuria (45/57). A comparison of the WHO classification of initial and repeat biopsies showed evolution to another class in 23 instances, but more commonly a change within a class was seen. A decrease in proliferative lesions (classes III and IV and subsets of V) was noted on repeat biopsies. The chronicity index increased significantly (p = 0.0001) and the activity index decreased (p = 0.064) between biopsies. Seventy-seven percent of patients had a change in treatment based on biopsy results. CONCLUSION: The major reason for repeat renal biopsy in patients with SLE was proteinuria. Renal morphology in patients with SLE can change with time, particularly in terms of chronicity and activity features. Repeat biopsies in patients with SLE appear to have clinical utility.

Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus.

OBJECTIVE: To ascertain the relative effect of antimalarial (AM) agents on fasting lipid fractions in patients with systemic lupus erythematosus (SLE). METHODS: The study was cross sectional including all patients with SLE who were seen in our lupus clinic with fasting lipid profiles measured as part of evaluation from November 1995 to March 1999. RESULTS: A total of 123 patients with a mean age of 45.3 years and mean disease duration 13.4 years were studied; 73.2% were taking prednisone with a mean +/- SD dose of 10.9 +/- 9.2 mg/day, 48.0% were taking AM, and 30.8% were taking both. In the entire group, patients taking AM had a 12.5% lower total cholesterol (TC) (5.11 +/- 1.27 vs 5.84 +/- 1.23; p = 0.002), 22.1% lower very low density lipid-cholesterol (VLDL-C) (0.66 +/- 0.40 vs 0.85 +/- 0.39; p = 0.01), and 15.7% lower LDL-C (3.01 +/- 1.14 vs 3.58 +/- 1.10; p = 0.007). For patients taking prednisone, those taking concomitant AM (n = 38) had significantly lower TC (5.26 +/- 1.30 vs 5.99 +/- 1.29; p = 0.01), VLDL-C (0.65 +/- 0.39 vs 0.85 +/- 0.41; p = 0.02), and LDL-C (3.05 +/- 1.20 vs 3.69 +/- 1.09; p = 0.01) than those without AM (n = 48). For patients taking < or = 10 mg/day prednisone, TC (4.69 +/- 0.88 vs 5.74 +/- 1.20; p < 0.001), VLDL-C (0.61 +/- 0.37 vs 0.83 +/- 0.44; p = 0.05), and LDL-C (2.57 +/- 0.76 vs 3.49 +/- 1.04; p < 0.001) were still lower in patients with concomitant AM (n = 22) than those without AM (n = 36). CONCLUSION: TC, VLDL-C, and LDL-C levels were significantly lower in patients taking AM, including patients taking concomitant prednisone. Thus AM may have beneficial effects in SLE in addition to disease suppression.

Accurately describing changes in disease activity in Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores correlate with the clinician's impression of level of disease activity. METHODS: In total, 230 patients with SLE followed at the University of Toronto Lupus Clinic who had 5 visits 3 months apart in 1992-93 were studied. At each visit a standard protocol was completed. A clinician who did not know the patients or their SLEDAI scores evaluated each patient record and assigned a clinical activity level. "Flare" was defined by new or increased therapy for active disease, an expression of concern, or use of the term "flare" in the physician's notes. The SLEDAI score was calculated from the database. RESULTS: SLEDAI scores described a range of clinical activity as recognized by the clinician. Median SLEDAI scores ranged from 2 (inactive disease) to 8 (persistently active or flare). When the clinician assessed the patient to be improved, the median SLEDAI score decreased by 2. When the clinician assessed that the patient was experiencing a flare, the SLEDAI score increased by a median of 4. CONCLUSION: Based on our data we propose the following outcomes for patients with SLE: flare, an increase in SLEDAI > 3; improvement is a reduction in SLEDAI of > 3; persistently active disease is change in SLEDAI +/- 3; and remission a SLEDAI of 0. These outcomes will allow a more complete description of a patient's response to therapeutic intervention in a responder index.

Vascular events in hypertensive patients with systemic lupus erythematosus.

Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE. SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy-related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event. One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (p = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4-24.8, P < 0.001). We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia.

Natural history of hypercholesterolemia in systemic lupus erythematosus.

OBJECTIVE: To determine the natural history of hypercholesterolemia in the first 3 years of disease in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single center and to determine the influence of hypercholesterolemia on the subsequent development of coronary artery disease (CAD) related events. METHODS: We identified patients who were seen at the University of Toronto lupus clinic within 1 year of diagnosis from January 1, 1974, to December 31, 1987, and who were seen at least once a year in the first 3 years. Patients were divided into 3 groups: Normal cholesterol: serum total cholesterol (TC) < 5.2 mmol/l throughout the 3 year period of study. Sustained hypercholesterolemia: at least one measurement of TC of > 5.2 mmol/l in each of the first 3 years at the clinic. Variable hypercholesterolemia: TC > 5.2 mmol/l in no more than 2 of the first 3 years of followup. Patients were followed from inception until the present day. The primary outcome was the time of the first CAD related event (myocardial infarction, angina, or sudden unexplained death). RESULTS: One hundred thirty-four patients (118 women, 16 men) were studied: 33 (24.6%) had normal cholesterol, 54 (40.3%) had sustained hypercholesterolemia, and 47 (35.1%) had variable hypercholesterolemia. Using multiple logistic regression the best predictors of sustained hypercholesterolemia were cumulative dose of steroids, no antimalarial therapy, and age of onset of SLE > 35 years old. CAD related events occurred in 1 (3%) of the normal TC group, 3 (6.4%) of the variable group, and in 15 (27.8%) of the sustained group (p = 0.003), 79% of all CAD events occurred in the sustained group. The best predictors of CAD were sustained hypercholesterolemia, lung involvement, and age at onset of SLE > 35 years. CONCLUSION: Within 3 years of diagnosis, 75.4% of patients with SLE had elevated TC, which was sustained in 40.3% of all patients. Older age at onset as well as increased cumulative dose of steroids and no antimalarial therapy are significant predictors of this group. It is this group that experiences the majority of CAD related events. Aggressive lipid lowering therapy should be targeted at such patients.

Extrarenal disease activity in systemic lupus erythematosus is not suppressed by chronic renal insufficiency or renal replacement therapy.

OBJECTIVE: To assess whether chronic renal impairment (CRI) and/or renal replacement therapy (RRT) in systemic lupus erythematosus (SLE) are associated with reduced extrarenal SLE activity. METHODS: This was a retrospective cohort analysis of patients with SLE who are followed at the University of Toronto Lupus Clinic. Patients with SLE were studied in 2 stages; chronic renal insufficiency (defined as a serum creatinine > 200 mumol/1 for > 6 months) and following the institution of dialysis therapy. Controls consisted of the next 2 age and sex matched patients in the clinic with a history of lupus nephritis who had not developed renal insufficiency. We assessed the flare rate (an increase in nonrenal SLEDAI > or = 1.0) for patients and controls in the first 12 months of followup at the clinic in each stage. RESULTS: Twenty-one patients, 17 female and 4 male, were followed through 25 episodes of CRI or RRT as were 50 controls. In the CRI stage (n = 12), flares occurred in 8 (67%) within one year compared to 14 (58%) of 24 controls (p = NS). In the RRT stage (n = 13), flares occurred in 7 (54%) compared to 16 (62%) of 26 controls (p = NS). The magnitude as well as the characteristics of the flares did not differ between patients and controls in either stage. CONCLUSION: Patients with SLE who develop CRI, or who receive RRT, continue to display evidence of ongoing extrarenal disease activity. Such patients require careful longterm followup for management of their extrarenal disease.

Factors associated with fatigue in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the relation between fatigue, disease activity, damage, and quality of life measures in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive patients attending the University of Toronto Lupus Clinic were studied. Disease activity was assessed using the SLEDAI and SLAM-R and damage using the SLICC/ACR Damage index. Fatigue was measured by the Fatigue Severity Score (FSS) and health status by the SF-36 questionnaire. In all cases a tender point count was also performed. RESULTS: 81 patients were studied. Their mean (SD) age and disease duration were 43 (12.5) years and 12.7 (8.0) years respectively. The FSS did not correlate with the SLEDAI nor with the SLAM-R. There was no correlation with the SLICC damage index. Fatigue severity correlated with the tender point count (SCC r=0.46, p<0.001), and negatively with all domains of the SF36 (r values -0.50 to -0.82). Disease activity and damage accounted for only 4.8% and 4% respectively of the variance in fatigue severity reported by patients. CONCLUSION: In an outpatient population of SLE patients, fatigue severity correlates with poor health status and a higher tender point count. In patients with SLE, factors associated with quality of life and fibromyalgia seem to have a greater influence on the severity of reported fatigue than does the level of current disease activity.

The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs.

OBJECTIVE: To examine the relationship between antimalarial therapy and total cholesterol in patients with systemic lupus erythematosus (SLE) with or without steroid therapy. METHODS: Retrospective study for the University of Toronto Lupus Clinic database between 1976 and 1997. The effects of antimalarials on random total cholesterol levels were assessed in the following situations: patients not receiving steroids (part I) that either initiated or discontinued antimalarials; patients receiving steroids (part II) that were either on a stable dose or initiating antimalarials; and patients initiating steroids with or without antimalarials (part III). Paired t test, Fisher's exact test, and 2 way analysis of variance were used when appropriate. RESULTS: Initiation of antimalarials reduced the baseline total cholesterol by 4.1 % at 3 months in 53 patients (p = 0.020) and by 0.6% at 6 months in 30 patients (p = NS), while the cessation of antimalarials increased the total cholesterol by 3.6% at 3 months in 38 patients (p = NS) and 5.4% at 6 months in 22 patients (p = NS). In 181 patients taking steroids and antimalarials, the mean total cholesterol was 11% less than for 201 patients receiving a comparable dose of steroids alone (p = 0.0023). Initiation of antimalarials on a stable dose of steroids reduced the total cholesterol by 11.3% at 3 months in 29 patients (p = 0.0002) and 9.4% at 6 months in 20 patients (p = 0.004). For patients initiating steroids, the percentage increase in cholesterol was lower in those taking antimalarials compared to patients without antimalarial therapy (p = 0.0149). CONCLUSION: Antimalarials lower total cholesterol in patients receiving steroids and may minimize steroid induced hypercholesterolemia.