ABSTRACT
OBJECTIVE: To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined. METHODS: This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage. RESULTS: A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage. CONCLUSIONS: BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.
Subject(s)
Heart Disease Risk Factors , Lupus Erythematosus, Systemic , Humans , Longitudinal Studies , Severity of Illness Index , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapyABSTRACT
AIM: The aim was to assess the health utility of lung metastasectomy in the treatment of patients with colorectal cancer (CRC) using the EQ-5D-3L questionnaire. METHODS: Multidisciplinary CRC teams at 14 sites recruited patients to a two-arm randomized controlled trial-Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC). Remote randomization was used, stratified by site and with minimization for seven known confounders. Participants completed the EQ-5D-3L questionnaire together with other patient reported outcome measures at randomization and then again at 3, 6, 12 and 24 months. These were returned by post to the coordinating centre. RESULTS: Between December 2010 and December 2016, 93 participants were randomized, 91 of whom returned questionnaires. Survival and patient reported quality of life have been published previously, revealing no significant differences between the trial arms. Described here are patient reported data from the five dimensions of the EQ-5D-3L and the visual analogue scale (VAS) health state. No significant difference was seen at any time point. The estimated difference between control and metastasectomy patients was -0.23 (95% CI -0.113, 0.066) for the composite 0 to 1 index scale based on the descriptive system and 0.123 (95% CI -7.24, 7.49) for the 0 to 100 VAS scale. CONCLUSIONS: Following lung metastasectomy for CRC, no benefit was demonstrated for health utility, which alongside a lack of a survival or quality of life benefit calls into question the widespread use of the procedure.
Subject(s)
Colorectal Neoplasms , Metastasectomy , Colorectal Neoplasms/surgery , Humans , Lung , Quality of Life , Surveys and QuestionnairesABSTRACT
AIM: We wanted to examine survival in patients with resected colorectal cancer (CRC) whose lung metastases are or are not resected. METHODS: Teams participating in the study of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) identified potential candidates for lung metastasectomy and invited their consent to join Stage 1. Baseline data related to CRC and fitness for surgery were collected. Eligible patients were invited to consent for randomization in the PulMiCC randomized controlled trial (Stage 2). Sites were provided with case report forms for non-randomized patients to record adverse events and death at any time. They were all reviewed at 1 year. Baseline and survival data were analysed for the full cohort. RESULTS: Twenty-five clinical sites recruited 512 patients from October 2010 to January 2017. Data collection closed in October 2020. Before analysis, 28 patients with non-CRC lung lesions were excluded and three had withdrawn consent leaving 481. The date of death was known for 292 patients, 136 were alive in 2020 and 53 at earlier time points. Baseline factors and 5-year survival were analysed in three strata: 128 non-randomized patients did not have metastasectomy; 263 had elective metastasectomy; 90 were from the randomized trial. The proportions of solitary metastases for electively operated and non-operated patients were 69% and 35%. Their respective 5-year survivals were 47% and 22%. CONCLUSION: Survival without metastasectomy was greater than widely presumed. Difference in survival appeared to be largely related to selection. No inference can be drawn about the effect of metastasectomy on survival in this observational study.
Subject(s)
Colorectal Neoplasms , Lung Neoplasms , Metastasectomy , Cohort Studies , Humans , Lung Neoplasms/surgery , Risk FactorsABSTRACT
OBJECTIVES: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. RESULTS: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001). CONCLUSIONS: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.
Subject(s)
Lupus Erythematosus, Systemic/psychology , Lupus Vasculitis, Central Nervous System/psychology , Adult , Female , Humans , Longitudinal Studies , Lupus Erythematosus, Systemic/mortality , Lupus Vasculitis, Central Nervous System/mortality , Male , Middle Aged , Models, Statistical , Multilevel Analysis , Prospective Studies , Quality of LifeABSTRACT
For rheumatic diseases, Minimal Disease Activity (MDA) is usually defined as a composite outcome which is a function of several individual outcomes describing symptoms or quality of life. There is ever increasing interest in MDA but relatively little has been done to characterise the pattern of MDA over time. Motivated by the aim of improving the modelling of MDA in psoriatic arthritis, the use of a two-state model to estimate characteristics of the MDA process is illustrated when there is particular interest in prolonged periods of MDA. Because not all outcomes necessary to define MDA are measured at all clinic visits, a partially hidden multi-state model with latent states is used. The defining outcomes are modelled as conditionally independent given these latent states, enabling information from all visits, even those with missing data on some variables, to be used. Data from the Toronto Psoriatic Arthritis Clinic are analysed to demonstrate improvements in accuracy and precision from the inclusion of data from visits with incomplete information on MDA. An additional benefit of this model is that it can be extended to incorporate explanatory variables, which allows process characteristics to be compared between groups. In the example, the effect of explanatory variables, modelled through the use of relative risks, is also summarised in a potentially more clinically meaningful manner by comparing times in states, and probabilities of visiting states, between patient groups.
Subject(s)
Disease Progression , Quality of Life , Rheumatic Diseases , Algorithms , Data Interpretation, Statistical , Female , Humans , Male , Models, StatisticalABSTRACT
OBJECTIVE: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. RESULTS: There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. CONCLUSION: LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN.
Subject(s)
Ethnicity , Lupus Nephritis/ethnology , Outcome Assessment, Health Care , Adult , Disease Progression , Female , Follow-Up Studies , Global Health , Humans , Incidence , Lupus Nephritis/diagnosis , Male , Prospective Studies , Quality of Life , Risk Factors , Surveys and Questionnaires , Survival Rate/trendsABSTRACT
In psoriatic arthritis, many patients do not develop permanent joint damage even after a prolonged follow-up. This has led several authors to consider the possibility of a subpopulation of stayers (those who do not have the propensity to experience the event of interest), as opposed to assuming the entire population consist of movers (those who have the propensity to experience the event of interest). In addition, it is recognised that the damaged joints process may act very differently across different joint areas, particularly the hands, feet and large joints. From a clinical perspective, interest lies in identifying possible relationships between the damaged joints processes in these joint areas for the movers and estimating the proportion of stayers in these joint areas, if they exist. For this purpose, this paper proposes a novel trivariate mover-stayer model consisting of mover-stayer truncated negative binomial margins, and patient-level dynamic covariates and random effects in the models for the movers and stayers, respectively. The model is then extended to have a two-level mover-stayer structure for its margins so that the nature of the stayer property can be investigated. A particularly attractive feature of the proposed models is that only an optimisation routine is required in their model fitting procedures. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Subject(s)
Arthritis, Psoriatic/complications , Joint Diseases/etiology , Biometry , Humans , Models, StatisticalABSTRACT
OBJECTIVE: The aim of this study was to describe the outcomes and predictors for development of damage in a large inception cohort of SLE patients. METHODS: This was a prospective longitudinal study of a cohort of SLE patients. SLE patients were included if they were recruited within 3 years of achieving the fourth ACR criterion for SLE. Data were collected on disease activity, damage and treatment. Information on death was provided by the Office for National Statistics. The censoring date for analysis was 31 December 2010. A standardized mortality ratio was calculated. Poisson regression was used to determine the incidence rate for damage accrual. Multistate Markov modelling was used to determine predictors for development of damage. RESULTS: There were 382 patients (92.4% females, 51.6% Caucasian, 22% South Asian, 20.7% Afro-Caribbean) with 12 072 assessments and total follow-up of 2958 patient-years. There were 300 items of damage (in 143 patients) and 37 deaths. The overall standardized mortality ratio was 2.0 (95% CI 1.5, 2.8) and the most common causes of death were infection (37.8%), cardiovascular (27%) and malignancy (13.5%). The predictors for damage accrual were higher prior damage, older age at diagnosis, active disease, systemic corticosteroid exposure and CYC exposure. Patients were more likely to develop new damage earlier in their disease than later. Ethnicity was not predictive of damage accrual or death in this cohort. CONCLUSION: SLE patients have premature mortality. Active disease, corticosteroid exposure and CYC exposure were independently associated with the development of damage. Damage accrual is more likely to occur in early disease.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Cyclophosphamide/therapeutic use , Disability Evaluation , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/mortality , Severity of Illness Index , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Aged, 80 and over , Cohort Studies , Cyclophosphamide/adverse effects , Disease Progression , Female , Follow-Up Studies , Humans , Longitudinal Studies , Lupus Erythematosus, Systemic/epidemiology , Male , Middle Aged , Patient Outcome Assessment , Prospective Studies , Regression Analysis , Survival Rate , Treatment Outcome , United Kingdom/epidemiologyABSTRACT
OBJECTIVE: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) aims to establish the efficacy of 2 different ovarian cancer screening schedules. The psychosocial substudy examines the psychological factors associated with the screening program. METHODS: Women aged 50 to 75 years from 16 UK gynecologic centers randomized to annual multimodal screening or ultrasound screening (US) groups were followed up for 7 years. Psychosocial data from women who withdrew from the study after a repeat screen were examined. RESULTS: Sixteen percent (3499/21,733) of women requiring a repeat screening test in addition to annual screen withdrew from the study: 12.9% (1560/12,073) from the multimodal group and 20.1% (1939/9660) from the US group. An estimated relative risk of withdrawal is 1.46 (95% confidence interval, 1.36-1.56; P ≤ 0.001) for the US arm. High anxiety trait and increased psychological morbidity significantly influenced withdrawal, even when age, screening center, and group were taken into account (P < 0.001). The risk of withdrawal decreased significantly the longer a woman stayed in UKCTOCS, irrespective of the number of screens and intensity in the preceding year. CONCLUSIONS: Withdrawal rate was greater in women undergoing US screening and in those who had repeats earlier in UKCTOCS. Having a high predisposition to anxiety, high current state anxiety, and above threshold general psychological morbidity all increased the withdrawal rate.
Subject(s)
Anxiety/psychology , Early Detection of Cancer/psychology , Multimodal Imaging/methods , Ovarian Neoplasms/psychology , Aged , Female , Follow-Up Studies , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Prognosis , Psychology , Risk Factors , United Kingdom/epidemiologyABSTRACT
A generic random effects formulation for the Dirichlet negative multinomial distribution is developed together with a convenient regression parameterization. A simulation study indicates that, even when somewhat misspecified, regression models based on the Dirichlet negative multinomial distribution have smaller median absolute error than generalized estimating equations, with a particularly pronounced improvement when correlation between observations in a cluster is high. Estimation of explanatory variable effects and sources of variation is illustrated for a study of clinical trial recruitment.
Subject(s)
Clinical Trials as Topic/statistics & numerical data , Patient Selection , Regression Analysis , Biostatistics , Computer Simulation , Data Interpretation, Statistical , Humans , Linear Models , Longitudinal Studies , Models, StatisticalABSTRACT
OBJECTIVE: To examine the frequency and characteristics of headaches and their association with global disease activity and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE). METHODS: A disease inception cohort was assessed annually for headache (5 types) and 18 other neuropsychiatric (NP) events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 (SF-36) mental and physical component summary scores were collected. Time to first headache and associations with SF-36 scores were analyzed using Cox proportional hazards and linear regression models with generalized estimating equations. RESULTS: Among the 1,732 SLE patients enrolled, 89.3% were female and 48.3% were white. The mean ± SD age was 34.6 ± 13.4 years, duration of disease was 5.6 ± 5.2 months, and length of followup was 3.8 ± 3.1 years. At enrollment, 17.8% of patients had headache (migraine [60.7%], tension [38.6%], intractable nonspecific [7.1%], cluster [2.6%], and intracranial hypertension [1.0%]). The prevalence of headache increased to 58% after 10 years. Only 1.5% of patients had lupus headache, as identified in the SLEDAI-2K. In addition, headache was associated with other NP events attributed to either SLE or non-SLE causes. There was no association of headache with SLEDAI-2K scores (without the lupus headache variable), SDI scores, use of corticosteroids, use of antimalarials, use of immunosuppressive medications, or specific autoantibodies. SF-36 mental component scores were lower in patients with headache compared with those without headache (mean ± SD 42.5 ± 12.2 versus 47.8 ± 11.3; P < 0.001), and similar differences in physical component scores were seen (38.0 ± 11.0 in those with headache versus 42.6 ± 11.4 in those without headache; P < 0.001). In 56.1% of patients, the headaches resolved over followup. CONCLUSION: Headache is frequent in SLE, but overall, it is not associated with global disease activity or specific autoantibodies. Although headaches are associated with a lower HRQOL, the majority of headaches resolve over time, independent of lupus-specific therapies.
Subject(s)
Autoantibodies/blood , Headache/epidemiology , Headache/immunology , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/immunology , Adult , Cluster Headache/epidemiology , Cluster Headache/immunology , Female , Follow-Up Studies , Humans , Internationality , Intracranial Hypertension/epidemiology , Intracranial Hypertension/immunology , Kaplan-Meier Estimate , Male , Middle Aged , Migraine Disorders/epidemiology , Migraine Disorders/immunology , Proportional Hazards Models , Prospective Studies , Quality of Life , Tension-Type Headache/epidemiology , Tension-Type Headache/immunology , Young AdultABSTRACT
Multi-state models provide a convenient statistical framework for a wide variety of medical applications characterized by multiple events and longitudinal data. We illustrate this through four examples. The potential value of the incorporation of unobserved or partially observed states is highlighted. In addition, joint modelling of multiple processes is illustrated with application to potentially informative loss to follow-up, mis-measured or missclassified data and causal inference.
Subject(s)
Likelihood Functions , Longitudinal Studies/methods , Models, Statistical , Survival Analysis , Adult , Arthritis, Psoriatic/physiopathology , Arthritis, Psoriatic/psychology , Coronary Disease/epidemiology , Female , Humans , Male , Middle Aged , Quality of Life/psychologyABSTRACT
In many studies, interest lies in determining whether members of the study population will undergo a particular event of interest. Such scenarios are often termed 'mover-stayer' scenarios, and interest lies in modelling two sub-populations of 'movers' (those who have a propensity to undergo the event of interest) and 'stayers' (those who do not). In general, mover-stayer scenarios within data sets are accounted for through the use of mixture distributions, and in this paper, we investigate the use of various random effects distributions for this purpose. Using data from the University of Toronto psoriatic arthritis clinic, we present a multi-state model to describe the progression of clinical damage in hand joints of patients with psoriatic arthritis. We consider the use of mover-stayer gamma, inverse Gaussian and compound Poisson distributions to account for both the correlation amongst joint locations and the possible mover-stayer situation with regard to clinical hand joint damage. We compare the fits obtained from these models and discuss the extent to which a mover-stayer scenario exists in these data. Furthermore, we fit a mover-stayer model that allows a dependence of the probability of a patient being a stayer on a patient-level explanatory variable.
Subject(s)
Arthritis, Psoriatic/etiology , Arthritis, Psoriatic/pathology , Models, Biological , Biostatistics , Disease Progression , Hand Joints/pathology , Humans , Likelihood Functions , Models, Statistical , Poisson Distribution , ProbabilityABSTRACT
OBJECTIVE: To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort. METHODS: NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non-SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random-effects regressions. Five- and 10-year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling. RESULTS: A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non-SLE NP events, predicted annual, 5-, and 10-year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5-fold higher and indirect costs 1.3-fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non-SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs. CONCLUSION: Patients with new/ongoing SLE or non-SLE NP events incurred higher direct and indirect costs.
Subject(s)
Cerebrovascular Disorders , Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/therapy , Lupus Erythematosus, Systemic/complications , Longitudinal Studies , Ethnicity , WhiteABSTRACT
Time-to-event and similar analyses can be problematic if the event of interest is operationally defined by some condition being true for a prolonged period of time. A particular example of this, remission in psoriatic arthritis, is considered in detail for illustration. A 3-state model is proposed for characterizing the transition rates into and out of remission. Remission is linked to an initial and subsequent state for the purpose of introducing the condition that remission must be of some duration to be clinically meaningful. The model is compared with alternative approaches that have been used in such situations. These involve 2-state models where the duration of remission is allowed for through different definitions for the time of entry into remission. Both definitions are linked to prolonged observation of a particular clinical state.
Subject(s)
Arthritis, Psoriatic/pathology , Models, Biological , Models, Statistical , Remission, Spontaneous , HumansABSTRACT
OBJECTIVE: The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE). METHODS: The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-ß(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions. RESULTS: The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03). CONCLUSION: Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.
Subject(s)
Epilepsy/complications , Epilepsy/epidemiology , Lupus Erythematosus, Systemic/complications , Cohort Studies , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Risk FactorsABSTRACT
OBJECTIVE: To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. METHODS: Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. RESULTS: A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater's assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater's assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). CONCLUSION: The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients.
Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Pregnancy Complications/diagnosis , Adult , Cross-Sectional Studies , Ethnicity , Female , Humans , Pregnancy , Reproducibility of Results , Severity of Illness IndexABSTRACT
OBJECTIVE: This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. METHODS: Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. RESULTS: There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. CONCLUSION: The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required.
Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Severity of Illness Index , Adolescent , Adult , Aged , Data Display , Disease Progression , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Young AdultABSTRACT
OBJECTIVE: To compare the responsiveness of the British Isles Lupus Assessment Group 2004 index (BILAG-2004) and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity indices and to determine whether there was any added value in combining BILAG-2004, BILAG-2004 system tally (BST), or simplified BST (sBST) with SLEDAI-2K. METHODS: This was a multicenter longitudinal study of SLE patients. Data were collected on BILAG-2004, SLEDAI-2K, and therapy on consecutive assessments in routine practice. The external responsiveness of the indices was assessed by determining the relationship between change in disease activity and change in therapy between 2 consecutive visits. Comparison of indices and their derivatives was performed by assessing the main effects of the indices using logistic regression. Receiver operating characteristic curves analysis was used to describe the performance of these indices individually and in various combinations, and comparisons of area under the curve were performed. RESULTS: There were 1,414 observations from 347 patients. Both BILAG-2004 and SLEDAI-2K maintained an independent relationship with change in therapy when compared. There was some improvement in responsiveness when continuous SLEDAI-2K variables (change in score and score of previous visit) were combined with BILAG-2004 system scores. Dichotomization of BILAG-2004 or SLEDAI-2K resulted in poorer performance. BST and sBST had similar responsiveness as the combination of SLEDAI-2K variables and BILAG-2004 system scores. There was little benefit in combining SLEDAI-2K with BST or sBST. CONCLUSION: The BILAG-2004 index had comparable responsiveness to SLEDAI-2K. There was some benefit in combining both indices. Dichotomization of BILAG-2004 and SLEDAI-2K leads to suboptimal performance. BST and sBST performed well on their own; sBST is recommended for its simplicity and clinical meaningfulness.