The Sjögren's Syndrome Damage Index--a damage index for use in clinical trials and observational studies in primary Sjögren's syndrome.

OBJECTIVE: To validate a tool for assessment of accumulated damage in patients with Primary SS (PSS). METHODS: Of the total 114 patients fulfilling American-European Consensus Group (AECG) criteria for PSS 104 were included in the study and assessed by rheumatologists at T (time) = 0 months and T = 12 months. On each occasion, damage and activity data, and autoantibody status were collected. SF-36 and Profile of Fatigue and Discomfort-Sicca Symptoms Inventory (PROFAD-SSI) questionnaires were completed. Cross-sectional analysis of this data was subject to a process of expert validation by 11 ophthalmologists, 14 oral medicine specialists and 8 rheumatologists. Items were removed from the index if >or= 50% of respondents recommended exclusion. Statistical validation was performed on remaining items. Spearman's rank analysis was used to investigate associations between damage scores and other disease status measures and Wilcoxon matched-pair analysis to assess sensitivity to change in the damage score. RESULTS: Based on the expert validation, a 29-item damage score was agreed incorporating ocular, oral and systemic domains. Total damage score correlated with disease duration at study entry (r = 0.436; P < 0.001), physical function as measured by SF-36 (r = 0.250, T = 0 months; r = 0.261 T = 12 months) and activity as measured by the Sjögren's Systemic Clinical Activity Index (r = 0.213, T = 0 months; r = 0.215, T =12 months). Ocular damage score correlated with the 'eye dry' domain of PROFAD-SSI (r = 0.228, T = 0 months; r = 0.365, T = 12 months). Other associations not present on both assessments were considered clinically insignificant. On Wilcoxon analysis, the index was sensitive to change over 12 months (z = -3.262; P < 0.01). CONCLUSION: This study begins validation of a tool for collection of longitudinal damage data in PSS. We recommend further trial in both the experimental and clinical environment.

Sjögren's Systemic Clinical Activity Index (SCAI)--a systemic disease activity measure for use in clinical trials in primary Sjögren's syndrome.

OBJECTIVE: This article describes the development of the Sjögren's Systemic Clinical Activity Index (SCAI) for the measurement of systemic disease activity in patients with primary Sjögren's syndrome (PSS). METHODS: A pilot tool was developed based on expert consensus and previous published data. One hundred and four patients with PSS were evaluated in a cross-sectional analysis, of whom 65 were reviewed at 3-monthly intervals, using this index, over a 12-month period. Factor analysis was used to evaluate the proposed domain structure. External validation was assessed by comparison with relevant domains of the Profile of Fatigue and Discomfort (PROFAD), Medical Outcomes Study Short Form-36 (SF-36) and The World Health Organization Quality of Life-Bref (WHOQOL-BREF). Sensitivity to change was assessed by comparing SCAI-derived flares with physician-designated disease flare and intention-to-treat analysis. A reliability and repeatability workshop was also held. RESULTS: Factor analysis supported the proposed domain structure. There were strong correlations between the SCAI fatigue, musculoskeletal and Raynaud's components and the PROFAD fatigue, arthralgia and vascular domains. There was a significant correlation between change in therapy and SCAI-defined flares (P = 0.01). The mean kappa-test results both for reliability of the SCAI and for physician repeatability were 0.71. CONCLUSION: This initial evaluation supports the potential for the SCAI as a tool for systemic activity assessment in patients with PSS but additional work is required to assess sensitivity to change in clinical therapeutic trials.

Effect site concentration during propofol TCI sedation: a comparison of sedation score with two pharmacokinetic models.

Target controlled infusion (TCI) pumps function using a programme based on a pharmacokinetic/pharmacodynamic model. We compared the Marsh and Schnider models to find out which better correlates with the clinically observed effect of propofol as assessed by the Observer Assessment of Alertness/Sedation (OAAS) score and the Bispectral index. We assessed the sedation score and Bispectral index score in 40 un-premedicated patients undergoing surgical procedures under spinal anaesthesia with propofol sedation to a target concentration of 2 microg.ml(-1). Half of the patients received TCI propofol driven by the Schnider model in effect site control, the other half were sedated with TCI propofol driven by the Marsh model in plasma control. We calculated the effect site concentration predicted by both models for all the patients. Changes in the sedation score and Bispectral index correlated better with the Marsh than with the Schnider effect site prediction in both study groups.

Direct healthcare costs and predictors of costs in patients with primary Sjogren's syndrome.

OBJECTIVES: To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sjögren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. METHODS: A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. RESULTS: Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. CONCLUSION: This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.

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.

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.

Analysis of the relationship between disease activity and damage in patients with systemic lupus erythematosus--a 5-yr prospective study.

OBJECTIVE: To determine whether initial damage, disease duration, age, initial health status, average disease activity over the 5 yr or an average medication score covering the follow-up period would predict an increase in damage in patients with systemic lupus erythematosus (SLE) within the next 5 yr. METHODS: A 5-yr prospective longitudinal study of a cohort of 141 consecutive patients with SLE attending a specialist lupus out-patient clinic in London from their first assessment between July 1994 and February 1995. Disease activity was assessed using the BILAG system, initial health status by the Medical Outcome Survey Short Form 20 with an extra question about fatigue (SF-20+) and damage by the SLICC/ACR Damage Index (SDI). Damage was reassessed 5 yr later. Statistical analysis was carried out using multiple logistic regression analysis (logXact). RESULTS: One hundred and thirty-three female and eight male SLE patients (97 Caucasians, 16 Afro-Caribbeans, 22 Asians and 6 others) were included, their age at inclusion was 41.1 +/- 12.5 yr and their disease duration 10.2 +/- 6.3 yr. The mean measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2 (0-7) and medication score 1.2 (0-3). Six patients were lost to follow-up because they had moved. Of the remaining 135 patients total damage had increased in 40 patients and 10 patients had died. At the end of the study, at 4.63 +/- 0.19 yr, the total SDI had increased to 1.6 +/- 1.7. Multiple logistic regression analysis revealed that death and increase in damage were strongly predicted by a high total disease activity over the entire study period (P<0.001) as we had hypothesized. When the total BILAG score was replaced by the average number of A-flares the prediction of accrual of damage during the study period was again highly significant (P = 0.004). CONCLUSIONS: In this first prospective study of its type a highly significant impact of total disease activity, as measured over 5 yr using the BILAG system, on the development of total damage was revealed. Moreover, these results provide further proof of the validity of the SDI and support the BILAG concept of the A-flares.

Definition and treatment of lupus flares measured by the BILAG index.

OBJECTIVES: The BILAG index is a clinical measure of lupus disease activity. It is valid, reliable and sensitive to change. Scoring in the BILAG index is based upon the physician's intention to treat. A flare of active lupus is defined as a new A or B score in at least one system. The main aim of this study was to determine whether patients with a lupus flare are treated as expected from the principles upon which the scoring system was devised. Secondly we wanted to establish whether patients with a new B score preceded by a C should be considered to have flared, as with patients scoring B following a D or E score. METHODS: Over a 12-month period, 250 patients regularly attending lupus clinics in Birmingham and London were assessed using the BILAG index at each visit. RESULTS: A new A or B score was observed in 154 (61.6%) patients. An A flare was observed in 26 (10.4%) patients. A B flare (in which the B score was preceded by a D or E score) was observed in 65 (26.0%) patients. There were 63 (25.2%) patients in whom there was a B score in a system in which a C score was previously recorded. Steroids were started or increased in 20 (77%) patients with an A flare. Almost all (92%) patients with a new A score had some increase in therapy. For the patients with new B scores, 53 (41%) had some increase in therapy, but multiple reasons were found for no change in therapy in 75 (59%) of these patients. There was no difference in the treatment of new B scores arising after a previous C score compared with previous D or E scores. Non-Caucasians were more likely to have a lupus flare than Caucasians. CONCLUSIONS: These results are consistent with the principles upon which the BILAG index was devised and suggest that a moderate disease flare can be defined as a new B score following a C, D or E score according to the BILAG index.

Patient-maintained sedation for oral surgery using a target-controlled infusion of propofol - a pilot study.

OBJECTIVE: To assess the safety and efficacy of a new patient-maintained propofol system for conscious sedation in dentistry. DESIGN: Prospective clinical trial SETTING: Department of Sedation, Glasgow Dental Hospital and School, 2001 SUBJECTS AND METHODS: Patients scheduled for oral surgery with conscious sedation. Exclusions included ASA IV -V, inability to use the handset, opioid use and severe respiratory disease. INTERVENTIONS: Patients were given intravenous propofol to a level of 1.0 microg/ml (reducing from 1.5 microg/ml) using a target controlled infusion system, they then controlled their sedation level by double-clicking a handset which on each activation increased the propofol concentration by 0.2 microg/ml. MAIN OUTCOME MEASURES: Oxygen saturation, patient satisfaction, and surgeon satisfaction. RESULTS: Twenty patients were recruited, 16 female and four male. Nineteen patients completed sedation and treatment successfully. Mean lowest oxygen saturation was 94%. No patients were over-sedated. All patients successfully used the system to maintain a level of sedation adequate for their comfort. Patient and surgeon satisfaction were consistently high. CONCLUSIONS: Initial experience with this novel system has confirmed safety, patient satisfaction and surgeon satisfaction.

Clinical, immunological, and immunogenetic aspects of autoantibody production against Ro/SSA, La/SSB and their linear epitopes in primary Sjögren's syndrome (pSS): a European multicentre study.

OBJECTIVES: To investigate the clinical and immunogenetic aspects of antibody formation against Ro/SSA and La/SSB as well as their linear B cell epitopes in patients with primary Sjögren's syndrome (pSS) from different European countries. PATIENTS AND METHODS: Ninety patients with pSS from six European centres were studied. Serum samples from all patients were tested in a control laboratory for anti-Ro/SSA and anti-La/SSB autoantibodies by RNA precipitation assay and autoantibodies to the previously reported B cell linear epitopes of Ro 60 kDa (p169-190aa and p211-232aa) and La/SSB (p147-154aa, p291-302aa, p301-318aa, and p349-364aa). DNA from 88 patients was used for the determination of HLA-DRB1, -DQA1, and -DQB1 genotypes. Analysis of the results was performed in the 88 patients who were genotyped and tested also for antipeptide antibodies. RESULTS: Antibodies to B cell epitopes of Ro 60 kDa were detected at a low frequency (range 10-37%). In contrast, B cell epitopes of La/SSB were detected frequently (range 58-86%) among the anti-La/SSB positive sera. Autoantibodies to the La/SSB epitope, p349-364aa, were significantly positively associated with longer disease duration (p<0.05), recurrent or permanent parotid gland enlargement (p<0.005), and a higher proportion of non-exocrine manifestations (p<0.005), compared with patients without autoantibodies. The presence of anti-Ro/SSA and anti-La/SSB autoantibodies was significantly associated with the presence of HLA-DRB1*03 and DQB1*02 (p=0.038 and p=0.034, respectively). This association was even more prominent and extended to HLA-DQA1*0501 when patients were stratified according the presence of autoantibodies to discrete La/SSB B cell epitopes in comparison with autoantibody negative patients (p<0.01). They were found also to be highly associated with the alleles HLA-DQB1*02 and HLA-DQA1*0501 as well as the presence of a shared amino acid motif in the region 59-69aa of DQB1 first domain (p<0.01, respectively). CONCLUSIONS: Autoantibodies against La/SSB, binding to four synthetic peptides, derived from the sequence of the La protein were identified with increased frequency in sera of patients with pSS. The formation of autoantibodies against B cell epitope analogues of La/SSB in European patients with pSS may be dependent on the presence of a permissive HLA-DQ heterodimer, most prominently represented by the HLA-DQA1*0501/DQB1*0201 heterodimer, suggesting that a model of HLA restricted presentation of La/SSB peptide determinants is crucial for the autoimmune response against La/SSB.

A prospective randomized study of the potential benefits of thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass grafting.

We performed an open, prospective, randomized, controlled study of the incidence of major organ complications in 420 patients undergoing routine coronary artery bypass graft surgery with or without thoracic epidural anesthesia and analgesia (TEA). All patients received a standardized general anesthetic. Group TEA received TEA for 96 h. Group GA (general anesthesia) received narcotic analgesia for 72 h. Both groups received supplementary oral analgesia. Twelve patients were excluded-eight in Group TEA and four in Group GA-because of incomplete data collection. New supraventricular arrhythmias occurred in 21 of 206 patients (10.2%) in Group TEA compared with 45 of 202 patients (22.3%) in Group GA (P = 0.0012). Pulmonary function (maximal inspiratory lung volume) was better in Group TEA in a subset of 93 patients (P < 0.0001). Extubation was achieved earlier (P < 0.0001) and with significantly fewer lower respiratory tract infections in Group TEA (TEA = 31 of 206, GA = 59 of 202; P = 0.0007). There were significantly fewer patients with acute confusion (GA = 11 of 202, TEA = 3 of 206; P = 0.031) and acute renal failure (GA = 14 of 202, TEA = 4 of 206; P = 0.016) in the TEA group. The incidence of stroke was insignificantly less in the TEA group (GA = 6 of 202, TEA = 2 of 206; P = 0.17). There were no neurologic complications associated with the use of TEA. We conclude that continuous TEA significantly improves the quality of recovery after coronary artery bypass graft surgery compared with conventional narcotic analgesia.

Total costs and predictors of costs in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the annual direct, indirect and total costs and predictors of costs in patients with systemic lupus erythematosus (SLE). METHODS: One hundred and five patients with SLE completed questionnaires on health-care utilization and employment history. Predictors of costs were determined by multiple regression analyses using direct, indirect and total costs as outcome variables. Demographics, health status, disease activity, end-organ damage, social support and satisfaction with care were used as predictor variables. RESULTS: The mean annual total cost per patient was pounds sterling 7913. Direct costs were a third and indirect costs two-thirds of the total cost. Higher education level, greater disease activity and lower physical functioning were associated with higher direct, indirect and total costs. Higher direct costs were also associated with greater damage and younger age. CONCLUSION: SLE has a considerable impact on the health-care system and society. Improvement in disease activity and physical health and prevention of end-organ damage may reduce costs in SLE.

Effects of the auditory stimuli of an auditory evoked potential system on levels of consciousness, and on the bispectral index.

Investigators in the field of depth of anaesthesia monitoring sometimes measure the auditory evoked potential (AEP) and the Bispectral Index (BIS) concurrently. However, the auditory stimuli required to generate an AEP may increase the level of consciousness, and cause an increase in the BIS. They may also alter the BIS by producing phase-locked harmonics in the surface electroencephalogram. The aim of this study was to determine if AEP stimuli have clinically significant effects on levels of consciousness and BIS values during sedation and general anaesthesia. Ten healthy adult patients were studied by measuring and recording the BIS for 6 epochs of 5 min each. The first 3 epochs took place during steady-state sedation, during which time the Observer's Assessment of Awareness/Sedation (OAA/S) score was also measured. The second 3 epochs took place during steady-state anaesthesia. During alternate epochs, patients were subjected to the auditory stimuli generated by an AEP system. The auditory stimuli were not associated with a change in BIS values (during sedation and anaesthesia) or OAA/S scores (sedation).

Underestimating the value of women: assessing the indirect costs of women with systemic lupus erythematosus. Tri-Nation Study Group.

OBJECTIVE: Indirect costs result from diminished productivity and are incorporated in cost-benefit analysis to guide health resource allocation. Valuing the productivity impairment of those not involved in labor market activities is controversial but important for diseases affecting predominantly women if allocation decisions are to be economically efficient and equitable. We compared indirect costs incurred by women with systemic lupus erythematosus (SLE), a prototypical women's disease, calculated under varying assumptions for the value of diminished labor market and non-labor market activity. METHODS: Six hundred forty-eight female patients with SLE reported on employment status and time lost by themselves and their caregivers from labor market and non-labor market activities over a 6 month period. RESULTS: Average annual indirect costs ranged from $1,424 to $22,604 (1997 Canadian dollars) dependent on the value assigned to labor market and non-labor market activity. CONCLUSION: Indirect cost estimates that fail to consider longterm labor market absenteeism and diminished non-labor market productivity and do not use gender neutral wages to value labor market activity may lead to decisions that jeopardize resources for women's diseases.

Do present damage and health perception in patients with systemic lupus erythematosus predict extent of future damage?: a prospective study.

OBJECTIVE: To study whether either initial damage, disease activity, disease duration, age, a drug score, or health status would predict an increase in damage in patients with systemic lupus erythematosus (SLE) within the next three years. METHODS: A three year prospective longitudinal study of a cohort of 141 consecutive patients with SLE attending a specialist lupus outpatient clinic from their first assessment between July 1994 and February 1995. Disease activity was assessed using the BILAG system, health status by the Medical Outcome Survey Short Form 20 with an extra question about fatigue (SF-20+), and damage by the SLICC/ACR Damage Index (SDI). Damage was reassessed three years later. Statistical analysis was carried out using logistic regression analysis (logXact). RESULTS: 133 female and 8 male patients with SLE (97 white subjects, 16 Afro-Caribbeans, 22 Asians, and 6 others) were included. Their mean (SD) age at inclusion was 41.1 (12.5) years and their disease duration 10.2 (6. 3) years. The mean measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2 (0-7), drug score 1.2 (0-3); SF-20+: physical 58 (0-100), role 54 (0-100), social functioning 71 (0-100), mental health 64 (16-100), health perception 44 (0-100), pain 53 (0-100), fatigue 59 (0-100). Four patients were lost to follow up because they had moved. At three years in 33 patients the total SDI had increased to a mean of 1.5 (0-7) (n=130). Moreover, seven patients had the maximum damage as they had died during the follow up period. The only variables with an independent and significant contribution in predicting damage at three years were the total damage score (odds ratio (OR)=1.46; 95% CI 1.04 to 2.05), and health perception (OR=0.96; 95% CI 0.93 to 0.99) at inclusion. CONCLUSIONS: Of all the variables at inclusion only the total damage score and SF-20+: health perception, significantly predicted an increase in damage, for patients with SLE, three years later.