Prediction of Hospitalizations in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. METHODS: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. RESULTS: The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]). CONCLUSION: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

Neuropsychiatric Events in Systemic Lupus Erythematosus: Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort.

OBJECTIVE: To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: Upon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure. RESULTS: NP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001). CONCLUSION: In a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.

Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus.

OBJECTIVE: To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. METHODS: The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values. RESULTS: The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21. CONCLUSION: The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.

Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

OBJECTIVE: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. METHODS: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. RESULTS: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. CONCLUSION: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.

Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To evaluate the properties of a frailty index (FI), constructed using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, as a novel health measure in systemic lupus erythematosus (SLE). METHODS: For this secondary analysis, the baseline visit was defined as the first study visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36] scores) were assessed. The SLICC-FI was constructed using baseline data. The SLICC-FI comprises 48 health deficits, including items related to organ damage, disease activity, comorbidities, and functional status. Content, construct, and criterion validity of the SLICC-FI were assessed. Multivariable Cox regression was used to estimate the association between baseline SLICC-FI values and mortality risk, adjusting for demographic and clinical factors. RESULTS: In the baseline data set of 1,683 patients with SLE, 89% were female, the mean ± SD age was 35.7 ± 13.4 years, and the mean ± SD disease duration was 18.8 ± 15.7 months. At baseline, the mean ± SD SLICC-FI score was 0.17 ± 0.08 (range 0-0.51). Baseline SLICC-FI values exhibited the expected measurement properties and were weakly correlated with baseline SDI scores (r = 0.26, P < 0.0001). Higher baseline SLICC-FI values (per 0.05 increment) were associated with increased mortality risk (hazard ratio 1.59, 95% confidence interval 1.35-1.87), after adjusting for age, sex, steroid use, ethnicity/region, and baseline SDI scores. CONCLUSION: The SLICC-FI demonstrates internal validity as a health measure in SLE and might be used to predict future mortality risk. The SLICC-FI is potentially valuable for quantifying vulnerability among patients with SLE, and adds to existing prognostic scores.

Psychosis in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

OBJECTIVE: To determine, in a large, multiethnic/multiracial, prospective inception cohort of patients with systemic lupus erythematosus (SLE), the frequency, attribution, clinical, and autoantibody associations with lupus psychosis and the short- and long-term outcomes as assessed by physicians and patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including psychosis. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and the Short Form 36 (SF-36) were recorded. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,826 SLE patients, 88.8% were female and 48.8% were Caucasian. The mean ± SD age was 35.1 ± 13.3 years, the mean ± SD disease duration was 5.6 ± 4.2 months, and the mean ± SD follow-up period was 7.4 ± 4.5 years. There were 31 psychotic events in 28 of 1,826 patients (1.53%), and most patients had a single event (26 of 28 [93%]). In the majority of patients (20 of 25 [80%]) and events (28 of 31 [90%]), psychosis was attributed to SLE, usually either in the year prior to or within 3 years of SLE diagnosis. Positive associations (hazard ratios [HRs] and 95% confidence intervals [95% CIs]) with lupus psychosis were previous SLE NP events (HR 3.59 [95% CI 1.16-11.14]), male sex (HR 3.0 [95% CI 1.20-7.50]), younger age at SLE diagnosis (per 10 years) (HR 1.45 [95% CI 1.01-2.07]), and African ancestry (HR 4.59 [95% CI 1.79-11.76]). By physician assessment, most psychotic events resolved by the second annual visit following onset, in parallel with an improvement in patient-reported SF-36 summary and subscale scores. CONCLUSION: Psychosis is an infrequent manifestation of NPSLE. Generally, it occurs early after SLE onset and has a significant negative impact on health status. As determined by patient and physician report, the short- and long-term outlooks are good for most patients, although careful follow-up is required.

Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

OBJECTIVE: To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate. RESULTS: CerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non-SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE. CONCLUSION: CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE.

Clinical Challenges of Tacrolimus for Maintenance Immunosuppression Post-Lung Transplantation.

Lung transplantation (LTx) is a successful treatment option for end-stage lung disease, and immunosuppressant regimens, utilized to prevent rejection of the transplanted graft, are paramount to maintaining long-term graft survival. Immunosuppression can be classified as induction, maintenance, and antirejection therapy. This article focuses on maintenance immunosuppression that includes a combination of a calcineurin inhibitor (CNI), cell cycle inhibitor, and corticosteroid. CNIs remain the cornerstone of immunosuppression following LTx, and tacrolimus is now the preferred CNI, based on a better adverse effect profile and some limited evidence for enhanced efficacy. Tacrolimus is associated with a number of unique challenges post-LTx, with erratic and highly variable absorption making it difficult to achieve and maintain therapeutic levels. Current methods of therapeutic drug monitoring are extrapolated from models in liver and kidney transplants and are not validated in the LTx population. Alternative methods of delivering tacrolimus can address some of the issues associated with their use and can be utilized in particular clinical scenarios. Long-term toxicities attributed to tacrolimus, such as nephrotoxicity and neurotoxicity, can limit the long-term success of tacrolimus in preventing allograft rejection. This article emphasizes the current clinical challenges faced when managing LTx recipients with tacrolimus, offers strategies to manage these issues, and highlights the areas that need further research.

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Timely initiation of chemotherapy: a systematic literature review of six priority cancers - results and recommendations for clinical practice.

This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided.

Impact of concomitant medication use on belimumab efficacy and safety in patients with systemic lupus erythematosus.

Practicing physicians have requested efficacy and safety data for belimumab, when used with specific systemic lupus erythematosus (SLE) medications. This was a post hoc analysis of pooled efficacy and safety data from patients who received belimumab 10 mg/kg plus standard of care (SoC) or placebo (SoC) in two Phase III, randomized trials, BLISS-52 and BLISS-76. Patients were categorized into four groups based on baseline concomitant medication usage: steroids only; antimalarials (AM) only; steroids + AM; or steroids + AM + immunosuppressants (IS). The primary endpoint was the SLE Responder Index (SRI) at Week 52. SRI over time and individual SRI components were secondary endpoints. Time to first flare and changes in concomitant medications were exploratory endpoints. Safety was assessed using adverse event (AE) reporting. Across 834 patients, steroids + AM was the largest group (n = 346, 41.5%) and AM only was the smallest (n = 77, 9.2%). Disease duration was shortest in the steroids + AM group (5.7 years vs 6.4-7.1 years); SELENA-SLEDAI scores were similar across groups. At Week 52, the percentage of SRI responders was greatest in the steroids + AM group for belimumab 10 mg/kg (59%) compared with placebo (44%); treatment response and SRI component improvements were also observed across other groups. The probability of experiencing an SLE flare was reduced in the steroids-only group for patients who received belimumab 10 mg/kg compared with placebo (64.3% vs 78.1%; hazard ratio 0.64; 95% confidence interval: 0.42-0.96). There was little or no change in daily AM or IS dose in any group. For all groups, there was a general decrease in steroid dose over time; a quarter to a third of patients experienced decreased steroid doses at Week 52. The overall safety profile was similar across treatment arms and concomitant medication groups, with the exception of serious AEs in the steroids + AM group (belimumab 10 mg/kg 16%, placebo 8%). The efficacy and safety of belimumab in combination with SoC was demonstrated for various groupings of steroids, AM and IS. These findings may improve the understanding of the safety and efficacy of adding belimumab to different treatments.

Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens.

WHAT IS KNOWN AND OBJECTIVE: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. METHODS: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. RESULTS: Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). WHAT IS NEW AND CONCLUSION: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy.

The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials.

INTRODUCTION: Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus. METHODS: Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio). RESULTS: The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses. CONCLUSIONS: Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601.

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.

OBJECTIVE: To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. METHODS: The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. RESULTS: 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. CONCLUSIONS: In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.

A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach.

OBJECTIVE: To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30-60 ml/minute), or state 3 (<30 ml/minute) and estimated proteinuria state 1 (<0.25 gm/day), state 2 (0.25-3.0 gm/day), or state 3 (>3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration. RESULTS: Of 1,826 lupus patients, 700 (38.3%) developed LN. During a mean ± SD follow-up of 5.2 ± 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement. CONCLUSION: In LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations.

Integrating smoking cessation into routine care in hospitals--a randomized controlled trial.

AIMS: To evaluate the effectiveness of a pharmacist-led multi-component smoking cessation programme (GIVE UP FOR GOOD) compared with usual care in hospitalized smokers. DESIGN: Randomized, assessor-blinded, parallel-group trial. SETTING: Three tertiary public hospitals in Australia. PARTICIPANTS: A total of 600 adult in-patient smokers [mean ± standard deviation (SD), age 51 ± 14 years; 64% male] available for 12 months follow-up. INTERVENTIONS: Multi-component hospital pharmacist-led behavioural counselling and/or pharmacotherapy provided during hospital stay, on discharge and 1 month post-discharge, with further support involving community health professionals (n = 300). Usual care comprised routine care provided by hospitals (n = 300). MEASUREMENTS: Two primary end-points were tested using intention-to-treat analysis: carbon monoxide (CO)-validated 1-month sustained abstinence at 6-month follow-up and verified 6-month sustained abstinence at 12-month follow-up. Smoking status and pharmacotherapy usage were assessed at baseline, discharge, 1, 6 and 12 months. FINDINGS: Sustained abstinence rates for intervention and control groups were not significantly different at both 6 months [11.6% (34 of 294) versus 12.6% (37 of 294); odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.55-1.50] and 12 months [11.6% (34 of 292) versus 11.2% (33 of 294); OR = 1.04, 95% CI = 0.63-1.73]. Secondary end-points, self-reported continuous abstinence at 6 and 12 months, also agreed with the primary end-points. Use of pharmacotherapy was higher in the intervention group, both during hospital stay [52.3% (157 of 300) versus 42.7% (128 of 300); P = 0.016] and after discharge [59.6% (174 of 292) versus 43.5% (128 of 294); P < 0.001]. CONCLUSIONS: A pharmacist-led multi-component smoking cessation intervention provided during hospital stay did not improve sustained abstinence rates at either 6 or 12 months compared with routine hospital care.