Risk factors for transmission of carbapenem-resistant Enterobacterales to healthcare personnel gloves and gowns in the USA.

BACKGROUND: Hospitals are sources for acquisition of carbapenem-resistant Entero-bacterales (CRE), and it is believed that the contamination of healthcare personnel (HCP) hands and clothing play a major role in patient-to-patient transmission of antibiotic-resistant bacteria. AIM: The aim of this study was to determine which HCP types, HCP-patient interactions, and patient characteristics are associated with greater transmission of CRE to HCP gloves and gowns in the hospital. METHODS: This was a prospective observational cohort study that enrolled patients with recent surveillance or clinical cultures positive for CRE at five hospitals in four states in the USA. HCP gloves and gown were cultured after patient care. Samples were also obtained from patients' stool, perianal area, and skin of the chest and arm to assess bacterial burden. FINDINGS: Among 313 CRE-colonized patients and 3070 glove and gown cultures obtained after patient care, HCP gloves and gowns were found to be contaminated with CRE 7.9% and 4.3% of the time, respectively. Contamination of either gloves or gowns occurred in 10.0% of interactions. Contamination was highest (15.3%) among respiratory therapists (odds ratio: 3.79; 95% confidence interval: 1.61-8.94) and when any HCP touched the patient (1.52; 1.10-2.12). Associations were also found between CRE transmission to HCP gloves or gown and: being in the intensive care unit, having a positive clinical culture, and increasing bacterial burden on the patient. CONCLUSION: CRE transmission to HCP gloves and gown occurred frequently. These findings may inform evidence-based policies about what situations and for which patients contact precautions are most important.

Admission Laboratory Values Accurately Predict In-hospital Mortality: a Retrospective Cohort Study.

BACKGROUND: The greater the severity of illness of a patient, the more likely the patient will have a poor hospital outcome. However, hospital-wide severity of illness scores that are simple, widely available, and not diagnosis-specific are still needed. Laboratory tests could potentially be used as an alternative to estimate severity of illness. OBJECTIVE: To evaluate the ability of hospital laboratory tests, as measures of severity of illness, to predict in-hospital mortality among hospitalized patients, and therefore, their potential as an alternative method to severity of illness risk adjustment. DESIGNS AND PATIENTS: A retrospective cohort study among 38,367 adult non-trauma patients admitted to the University of Maryland Medical Center between November 2015 and November 2017 was performed. Laboratory tests (hemoglobin, platelet count, white blood cell count, urea nitrogen, creatinine, glucose, sodium, potassium, and total bicarbonate (HCO3)) were included when ordered within 24 h from the time of hospital admission. A multivariable logistic regression model to predict in-hospital mortality was constructed using a section of our cohort (n = 21,003). MAIN MEASURES: Model performance was evaluated using the c-statistic and the Hosmer-Lemeshow (HL) test. In addition, a calibration belt was constructed to determine a confidence interval around the calibration curve with the purpose of identifying ranges of miscalibration. KEY RESULTS: Patient age and all laboratory tests predicted mortality with good discrimination (c = 0.79). Patients with abnormal HCO3 levels or leukocyte counts at admission were twice as likely to die during their hospital stay as patients with normal results. A good model calibration and fit were observed (HL = 13.9, p = 0.18). CONCLUSIONS: Admission laboratory tests are able to predict in-hospital mortality with good accuracy, providing an objective and widely accessible approach to severity of illness risk adjustment.

Predictors of predominant Lupus Low Disease Activity State (LLDAS-50).

AIM: The Lupus Low Disease Activity State (LLDAS) is a potential treat to target goal in systemic lupus erythematosus (SLE). SLE patients in LLDAS for more than half of the observation time have about a 50% lower risk of new organ damage and have reduced mortality. We identified predictors of being in LLDAS ≥50% of the observation time. METHODS: A total of 2228 SLE patients who had at least three clinical visits were included. Percentage of time in LLDAS was calculated based on the proportion of days under observation. LLDAS-50 was defined as being in LLDAS for ≥50% of the observation time. We used the stepwise selection procedure in logistic regression to identify predictors of LLDAS-50. RESULTS: A total of 1169 (52.5%) SLE patients, but only 37.6% of African Americans, achieved LLDAS-50. In the multivariable model, African American ethnicity, hypocomplementemia, serositis, renal activity, arthritis, anti-RNP, anti-dsDNA, vasculitis, malar rash, discoid rash, thrombocytopenia, and immunosuppressive use were negative predictors of LLDAS-50. Older age at diagnosis, longer disease duration, higher education level, and greater percentage of time taking hydroxychloroquine remained positive predictors of LLDAS-50. CONCLUSION: In this large cohort, only 52.5% achieved LLDAS-50. This proportion was even less in African Americans. A higher percentage of time taking hydroxychloroquine was a modifiable positive predictor of LLDAS-50. Anti-RNP, anti-dsDNA, and low complement were negatively associated with LLDAS-50. Our findings further emphasize the importance of inclusion of African Americans in clinical trials and hydroxychloroquine adherence in both clinical practice and clinical trials.

Understanding systemic lupus erythematosus patients' desired outcomes and their perceptions of the risks and benefits of using corticosteroids.

Introduction The use of corticosteroids in systemic lupus erythematosus (SLE) patients requires difficult trade-offs between efficacy and risk of toxicity. This qualitative study examined SLE patients' most desired outcomes and their concerns with corticosteroid use in SLE treatment. Methods SLE patients with current/past experience with using corticosteroids were recruited from the clinics at the Johns Hopkins Lupus Center and the University of Maryland Medical Center. Five in-depth interviews ( N = 5) and four focus groups ( N = 15) were conducted during which discussions were transcribed and analyzed based on a grounded theory approach. Results We identified five major themes describing SLE patients' most desired outcomes: reduction in flares, maintenance of normal activities, minimization of treatment side effects, prevention of future organ damage, and finding a cure. Further, SLE patients reported these primary concerns with the adverse effects of corticosteroids: weight gain, organ damage (particularly bone-related damage), mood swings/irritability, sleep disturbances, and dental issues. Patients appeared to be more concerned with adverse effects that immediately affected their day-to-day lives. Conclusion Knowledge gained during this study better informs how patients view the benefits and risks of corticosteroids. This can facilitate discussions between physicians and patients as they work together to determine the appropriate use of corticosteroids.

Improving community ambulation after hip fracture: protocol for a randomised, controlled trial.

INTRODUCTION: After a hip fracture in older persons, significant disability often remains; dependency in functional activities commonly persists beyond 3 months after surgery. Endurance, dynamic balance, quadriceps strength, and function are compromised, and contribute to an inability to walk independently in the community. In the United States, people aged 65 years and older are eligible to receive Medicare funding for physiotherapy for a limited time after a hip fracture. A goal of outpatient physiotherapy is independent and safe household ambulation 2 to 3 months after surgery. Current Medicare-reimbursed post-hip-fracture rehabilitation fails to return many patients to pre-fracture levels of function. Interventions delivered in the home after usual hip fracture physiotherapy has ended could promote higher levels of functional independence in these frail and older adult patients. PRIMARY OBJECTIVE: To evaluate the effect of a specific multi-component physiotherapy intervention (PUSH), compared with a non-specific multi-component control physiotherapy intervention (PULSE), on the ability to ambulate independently in the community 16 weeks after randomisation. DESIGN: Parallel, two-group randomised multicentre trial of 210 older adults with a hip fracture assessed at baseline and 16 weeks after randomisation, and at 40 weeks after randomisation for a subset of approximately 150 participants. PARTICIPANTS AND SETTING: A total of 210 hip fracture patients are being enrolled at three clinical sites and randomised up to 26 weeks after admission. Study inclusion criteria are: closed, non-pathologic, minimal trauma hip fracture with surgical fixation; aged ≥ 60 years at the time of randomisation; community residing at the time of fracture and randomisation; ambulating without human assistance 2 months prior to fracture; and being unable to walk at least 300 m in 6minutes at baseline. Participants are ineligible if the interventions are deemed to be unsafe or unfeasible, or if the participant has low potential to benefit from the interventions. INTERVENTIONS: Participants are randomly assigned to one of two multi-component treatment groups: PUSH or PULSE. PUSH is based on aerobic conditioning, specificity of training, and muscle overload, while PULSE includes transcutaneous electrical nerve stimulation, flexibility activities, and active range of motion exercises. Participants in both groups receive 32 visits in their place of residence from a study physiotherapist (two visits per week on non-consecutive days for 16 weeks). The physiotherapists' adherence to the treatment protocol, and the participants' receipt of the prescribed activities are assessed. Participants also receive counselling from a registered dietician and vitamin D, calcium and multivitamin supplements during the 16-week intervention period. MEASUREMENTS: The primary outcome (community ambulation) is the ability to walk 300 m or more in 6minutes, as assessed by the 6-minute walk test, at 16 weeks after randomisation. Other measures at 16 and 40 weeks include cost-effectiveness, endurance, dynamic balance, walking speed, quadriceps strength, lower extremity function, activities of daily living, balance confidence, quality of life, physical activity, depressive symptoms, increase of ≥ 50 m in distance walked in 6minutes, cognitive status, and nutritional status. ANALYSIS: Analyses for all aims will be performed according to the intention-to-treat paradigm. Except for testing of the primary hypothesis, all statistical tests will be two-sided and not adjusted for multiple comparisons. The test of the primary hypothesis (comparing groups on the proportion who are community ambulators at 16 weeks after randomisation) will be based on a one-sided 0.025-level hypothesis test using a procedure consisting of four interim analyses and one final analysis with critical values chosen by a Hwang-Shih-Decani alpha-spending function. Analyses will be performed to test group differences on other outcome measures and to examine the differential impact of PUSH relative to PULSE in subgroups defined by pre-selected participant characteristics. Generalised estimating equations will be used to explore possible delayed or sustained effects in a subset of participants by comparing the difference between PUSH and PULSE in the proportion of community ambulators at 16 weeks with the difference at 40 weeks. DISCUSSION: This multicentre randomised study will be the first to test whether a home-based multi-component physiotherapy intervention targeting specific precursors of community ambulation (PUSH) is more likely to lead to community ambulation than a home-based non-specific multi-component physiotherapy intervention (PULSE) in older adults after hip fracture. The study will also estimate the potential economic value of the interventions.

Serum osteoprotegrin (OPG) in subclinical atherosclerosis in systemic lupus erythematosus.

Introduction Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor family. It has recently been demonstrated that OPG is produced by a variety of tissues, including the cardiovascular system (heart, arteries, veins), lung, kidney, immune tissues, and bone. The OPG-RANKL signaling pathway is strongly related to vascular calcification. We determined the association of this biomarker with subclinical atherosclerosis in systemic lupus erythematous (SLE). Methods We measured OPG and markers of subclinical atherosclerosis (coronary artery calcium (CAC), carotid intima-media thickness (cIMT) carotid plaque) in 166 SLE patients (91% female, 64% Caucasian, 31% African American, 5% others, mean age 45 years). Subgroups of patients with different levels of OPG level were compared with respect to average levels of CAC, cIMT, and with respect to presence of carotid plaque. Age was adjusted for using multiple regression. Results OPG was highly correlated with age ( p < 0.0001). Individuals with higher levels of OPG tended to have higher measures of CAC, cIMT, and more carotid plaque. However, after adjustment for age, these associations, while still positive, were no longer statistically significant. Conclusion In our study much of the association observed was due to confounding by age, and after adjusting for age, our findings do not rule out the possibility of a null association.

First-trimester prediction of pre-eclampsia: external validity of algorithms in a prospectively enrolled cohort.

OBJECTIVE: To evaluate the performance of published first-trimester prediction algorithms for pre-eclampsia (PE) in a prospectively enrolled cohort of women. METHOD: A MEDLINE search identified first-trimester screening-prediction algorithms for early-onset (requiring delivery < 34 weeks) and late-onset (requiring delivery ≥ 34 weeks) PE. Maternal variables, ultrasound parameters and biomarkers were determined prospectively in singleton pregnancies enrolled between 9 and 14 weeks. Prediction algorithms were applied to this population to calculate predicted probabilities for PE. The performance of the prediction algorithms was compared with that in the original publication and evaluated for factors explaining differences in prediction. RESULTS: Six early and two late PE prediction algorithms were applicable to 871-2962 women, depending on the variables required. The prevalence of early PE was 1.0-1.2% and of late PE was 4.1-5.0% in these patient subsets. One early PE prediction algorithm performed better than in the original publication (80% detection rate (DR) of early PE for 10% false-positive rate (FPR)); the remaining five prediction algorithms underperformed (29-53% DR). Prediction algorithms for late PE also underperformed (18-31% DR, 10% FPR). Applying the screening cut-offs based on the highest Youden index probability scores correctly detected 40-80% of women developing early PE and 71-82% who developed late PE. Exclusion of patients on first-trimester aspirin resulted in DRs of 40-83% and 65-82% for early and late PE, respectively. CONCLUSION: First-trimester prediction algorithms for PE share a high negative predictive value if applied to an external population but underperform in their ability to correctly identify women who develop PE. Further research is required to determine the factors responsible for the suboptimal external validity.

Oral candidiasis in systemic lupus erythematosus.

OBJECTIVES: We assessed the frequency of oral candidiasis and the association between demographic variables, disease-related variables, corticosteroid treatment, other treatments and the occurrence of oral candidiasis in the Hopkins Lupus Cohort. METHODS: In this large prospective cohort study of 2258 patients with systemic lupus erythematosus (SLE), demographic and clinical associates of oral candidiasis were estimated by univariate, multivariate and within-person regression models. RESULTS: There were 53,548 cohort visits. Oral candidiasis was diagnosed at 675 visits (1.25%) in 325 (14%) of the patients. In the multivariate analyses, oral candidiasis was associated with African-American ethnicity, SELENA-SLEDAI disease activity, high white blood cell count, a history of bacterial infection, prednisone use and immunosuppressive use. The urine protein by urine dip stick was higher in SLE patients with oral candidiasis. Considering only patients who had candidiasis at some visits in a 'within-person' analysis, candidiasis was more frequent in visits with higher SELENA-SLEDAI disease activity, high white blood cell count, proteinuria by urine dip stick, a history of bacterial infection and prednisone use. The use of hydroxychloroquine was associated with a lower risk of oral candidiasis, but was not statistically significant (p = 0.50) in the within-person analysis models. CONCLUSION: This study identified multiple risk factors for oral candidiasis in SLE. Inspection of the oral cavity for signs of oral candidiasis is recommended especially in SLE patients with active disease, proteinuria, high white blood cell count, taking prednisone, immunosuppressive drugs or antibiotics.

Outcomes of living versus deceased donor liver transplantation for acute liver failure in the United States.

Clinical outcomes for living donor liver transplantation (LDLT) for acute liver failure (ALF) in the United States remain to be determined. To address this gap in knowledge, we examined post-liver transplantation outcomes of adults with ALF undergoing LDLT and deceased donor liver transplantation (DDLT) in the United States. We analyzed Organ and Procurement and Transplantation Network data for adults with ALF who were listed for liver transplantation as status 1 or 1A and who underwent LDLT (N = 21) or DDLT (N = 2316) between October 1987 and April 2011. We found no strong evidence that the survival probabilities for adults with ALF who underwent LDLT were inferior to those who underwent DDLT (P = .764). In adults with ALF who underwent LDLT, 1- and 5-year survival probabilities were both 71%; for DDLT these probabilities were 79% and 71%, respectively. In adults with ALF, 1- and 5-year liver graft survival probabilities, respectively, were 62% and 57% for LDLT, and 74% and 66% for DDLT. In these series of adults with ALF who were listed as status 1 or 1A, patient and graft survival rates for LDLT were similar to those for DDLT. Our findings suggest that if deceased donor livers are unavailable, LDLT is an acceptable option in experienced centers for adults with ALF.

Determinants of intrathoracic adipose tissue volume and associations with cardiovascular disease risk factors in Amish.

BACKGROUND AND AIM: Hypothesizing that intrathoracic fat might exert local effects on the coronary vasculature, we assessed the association of intrathoracic fat volume and its two subcomponents with coronary artery calcification (CAC) in 909 relatively healthy Amish adults. METHODS AND RESULTS: Intrathoracic fat, which is comprised of fat between the surface of the heart and the visceral epicardium (epicardial fat) and fat around the heart but outside of the fibrous pericardium (pericardial fat), was measured from electron beam CT scans. We examined the association between intrathoracic fat volume and cardiovascular disease risk factors in multivariate regression model. Fat volume in the epicardial and pericardial compartments were highly correlated with each other and with body mass index. Neither CAC extent nor CAC presence (Agatston score > 0) was associated with increased intrathoracic fat volume in sex-stratified models adjusting for age (p > 0.10). Intrathoracic fat volume was significantly correlated with higher systolic/diastolic blood pressure, pulse pressure, fasting glucose, insulin, triglyceride and lower high-density lipoprotein cholesterol in sex-stratified models adjusting for age (p < 0.05). However, associations were attenuated after further adjustment for body mass index. CONCLUSIONS: These data do not provide support for a significant role for intrathoracic fat in the development of CAC.

The American College of Rheumatology and the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus in two multiethnic cohorts: a commentary.

The authors offer some comments on the advantages and possible drawbacks of using the SLICC criteria in longitudinal observational studies and clinical trials after applying and comparing them to the ACR criteria in two multinational, multiethnic lupus cohorts.

Erythrocyte sedimentation rate is a predictor of renal and overall SLE disease activity.

OBJECTIVE: Our aim was to assess whether erythrocyte sedimentation rate (ESR) levels correlate with the level of disease activity at each visit and whether a change in ESR could be useful in predicting changes in disease activity. METHODS: Thousands of visits in a prospective systemic lupus erythematosus (SLE) cohort were analyzed to assess the association of ESR and level of disease activity. We explored whether ESR was cross-sectionally associated with disease activity, whether changes in ESR were associated with changes in disease activity, and whether changes in ESR predicted future changes in disease activity. Visits when patients had cancer, infection, pregnancy or were in renal failure were excluded. RESULTS: After adjusting for confounding factors, mild (25-50 mm/h), moderate (51-75 mm/h), and marked (>75 mm/h) elevations in ESR levels at a given visit correlated with the SELENA-SLEDAI, the Physician Global Assessment (PGA), fatigue, renal, joint, rash, serositis, hematological visual analogue scale (VAS), hematuria and proteinuria (p<0.0001) levels at that visit. A change in ESR between two visits was highly correlated with a concurrent change in PGA, renal, fatigue and joint VAS (p<0.0001). There was no statistically significant correlation between change in ESR between two visits and change in disease activity at a future visit. The subgroup analysis of patients who do not have anti-dsDNA and low complement levels as a feature of their disease showed ESR to be positively associated with SLEDAI, PGA, renal and joint VAS at that visit (p<0.0001), but there were few significant associations between changes in ESR and changes in disease activity. CONCLUSION: ESR is associated with disease activity in SLE measured by the SELENA-SLEDAI, the PGA, and with organ-specific activity including serositis, rash, joint, renal and hematological VAS. Grouping baseline ESR into four levels does associate with both global and organ-specific disease activity. A change in ESR between two visits was highly correlated with a change in PGA, renal, fatigue and joint VAS. In patients without anti-dsDNA and low complement levels, ESR was positively associated with SLEDAI, PGA, renal and joint VAS at the same visit. Until more specific biomarkers are validated, serial ESR does have some utility in following disease activity in SLE.

Predictors of corticosteroid tapering in SLE patients: the Hopkins Lupus Cohort.

PURPOSE: Organ damage in systemic lupus erythematosus (SLE) patients is highly associated with the use of corticosteroids. Doses of prednisone below 6 mg daily are associated with reduced organ damage. We now report on the largest prospective cohort study of predictors of prednisone tapering in SLE patients. METHODS: A total of 866 SLE patients (91% female, 50% Caucasian, 43% African-American, mean age 43 years) who consented for the Hopkins Lupus Cohort from 1987 through 2009 were included. The analysis was based on patient visits in which the previously prescribed dose of prednisone was 5 mg/day. We then examined the proportion of times the patient's dose was reduced to below 5 mg/day ("tapering"). Among those patients who tapered and were followed for at least one year thereafter, we examined the proportion whose prednisone dose remained below 5 mg/day for at least one year ("Successful tapering"). Rates of tapering and successful tapering were calculated for patient subsets based on demographic and clinical characteristics. RESULT: The analyses showed that Caucasians, younger patients, patients with a higher level of education, lower disease activity, or absence of urine protein were more likely to have a prednisone taper. However, successful tapering was not dependent on age, ethnicity, or education. As expected, successful tapering was more frequent in those with lower disease activity. Successful tapering was achieved more often after the year 2000. CONCLUSION: Our study suggests that successful tapering of prednisone below 5 mg has increased since the year 2000, which may reflect the greater knowledge of the long-term harm of even low-dose chronic corticosteroid use. Caucasians, younger age, higher level of education, and absence of proteinuria predicted tapering, but not successful tapering. Ongoing cutaneous or arthritis activity were associated with unsuccessful tapering. Lack of disease activity, as expected, was the only major clinical variable that significantly predicted successful tapering.

Simultaneous liver-kidney versus liver transplantation alone in patients with end-stage liver disease and kidney dysfunction not on dialysis.

BACKGROUND: Since implementation of the Model for End-stage Liver Disease (MELD), the number of simultaneous liver-kidney transplantations (SLKT) has increased in the United States. However, predictors and survival benefit of SLKT compared to liver transplantation alone (LTA) are not well defined. METHODS: Organ Procurement and Transplantation Network data of patients with end-stage liver disease (ESLD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) who had not been on dialysis while on the waiting list and underwent liver transplantation between 2002 and 2008 were analyzed. To identify predictors of undergoing SLKT versus LTA, multiple logistic regression analysis was performed. Cox proportional hazards regression analysis was used to assess the association between SLKT and post-liver transplant patient and graft survival. RESULTS: The study cohort comprised 5443 patients; 262 (5%) underwent SLKT and 5181 (95%) underwent LTA. Adjusting for potential confounders, patients who underwent SLKT were 34% less likely to die after liver transplantation than those who underwent LTA (hazard ratio [HR] = 0.66, P = .012) and 33% less likely to have liver graft failure than those who underwent LTA (HR = 0.67, P = .010). Among those who underwent SLKT, 1-, 3-, and 5-year kidney graft survival probabilities were 88%, 80%, and 77%, respectively. Black race and diabetes were associated with a higher likelihood of SLKT versus LTA; female sex, a higher eGFR, and higher MELD score reduced the likelihood of SLKT. CONCLUSIONS: Among those with ESLD and kidney dysfunction not on dialysis, post-liver transplant patient and liver graft survivals of patients who underwent SLKT were superior to those of patients who underwent LTA. Whether this reflects differences in the two groups that could not be adjusted in survival models or a specific effect of kidney dysfunction cannot be established.

Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers.

OBJECTIVE: Autoantibodies are important in the diagnosis and classification of systemic lupus erythematosus (SLE), but whether they correlate with changes in disease activity within individual patients is controversial. We assessed the association between changes in SLE global and renal activity and changes in several autoantibodies and cell adhesion molecules in patients with SLE. METHODS: Stored sera collected at two or three clinic visits from each of 49 SLE patients (91% female, 59% African-American, 31% Caucasian, 10% other ethnicity, 38% under 30 years, 41% between 30-44 years, and 21% 45-63 years) were analyzed. The visits were chosen to include one visit with proteinuria, and one or two without, for each patient. Global disease activity was measured by the Physician's Global Assessment (PGA), SELENA-SLEDAI (SLE Disease Activity Index modified to exclude anti-dsDNA and complement) and renal activity assessed by urine protein (by urine dipstick) and Renal Activity Score. Sera were assayed for anti-C1q, anti-chromatin, anti-dsDNA, anti-ribosomal P, monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule (VCAM) intercellular adhesion molecule (ICAM) and complement. The associations between changes in disease activity and changes in biomarker levels were assessed. RESULTS: In terms of global disease activity, anti-C1q had the highest association with the PGA (p = 0.09) and was strongly associated with modified SELENA-SLEDAI (p = 0.009). In terms of renal activity, anti-C1q had the highest association with proteinuria (p = 0.079), and was strongly associated with Renal Activity Score (p = 0.006). CONCLUSION: Anti-C1q performed the best of the potential biomarkers, being significantly associated with the modified SELENA-SLEDAI and with the Renal Activity Score. This study indicates the potential superior utility of anti-C1q over anti-dsDNA and other measures to track renal activity.

Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity.

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.

Lupus Atherosclerosis Prevention Study (LAPS).

BACKGROUND: Cardiovascular disease is one of the major causes of death in systemic lupus erythematosus (SLE). A study was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. METHODS: 200 patients with SLE without clinical cardiovascular disease were randomised to receive atorvastatin 40 mg daily or an identical placebo. At baseline and after 2 years of follow-up, helical CT scanning (for coronary artery calcium) and carotid duplex (for intima media thickness/plaque) were performed. Patients were seen for measures of disease activity at 1 month, 3 months and quarterly thereafter. The primary outcome variable was change in coronary artery calcium. RESULTS: At baseline, 43% had coronary artery calcium. At 2 years there was no significant difference between the groups in progression of coronary artery calcium, carotid intima media thickness or carotid plaque. There was no significant difference between the groups in disease activity, measures of inflammation or endothelial cell activation. CONCLUSION: This study provides no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not appear to reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial. Clinicaltrials.gov (NCT 00120887).

Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy.

To develop diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), a retrospective series of patients' records diagnosed by sexpert consensus as CIDP or other chronic polyneuropathies were analyzed. Classification and regression tree analysis was applied to 150 patients to derive a classification rule. According to the rule, diagnosis of CIDP required that a patient have a chronic non-genetic polyneuropathy, progressive for at least eight weeks, without a serum paraprotein and either 1) recordable compound muscle action potentials in > or =75% of motor nerves and either abnormal distal latency in >50% of nerves or abnormal motor conduction velocity in >50% of nerves or abnormal F wave latency in >50% of nerves; or 2) symmetrical onset of motor symptoms, symmetrical weakness of four limbs, and proximal weakness in > or =1 limb. When validated in 117 patients, the rule had 83% sensitivity (95% confidence interval 69%-93%) and 97% specificity (95% confidence interval 89%-99%) and performed better than published criteria.

High dose cyclophosphamide performs better than monthly dose cyclophosphamide in quality of life measures.

In spite of current therapies, the overall health status of patients with SLE is poor. High-dose cyclophosphamide (50 mg/kg for 4 days) with or without stem-cell rescue has been introduced as a new therapy for severe SLE, including renal and central nervous system (CNS)-SLE. Long-term durable responses have been found to be 40%. A randomised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide (750 mg/m squared bovine serum albumin) in patients with SLE who need cyclophosphamide for the first time. The primary outcome of the trial was complete clinical response. In this report, we compare the treatment groups with respect to quality of life. The patients in this study had a mean age of 35.3 +/- 10.1 years, were of Caucasian (35%), African-American (51%), Hispanic (8%) and Asian (6%) people, and 88% were women. The organ leading to treatment was renal lupus in 29%, CNS-lupus in 45% and other organs in 26%. Quality of life was measured at each visit using the Medical Outcome Study Short-Form 36 (SF-36). At 6 months, the patients in the high-dose cyclophosphamide trial arm had significantly greater improvement than patients in the monthly intravenous cyclophosphamide arm (P = 0.026; P = 0.0082, respectively) in the categories of general health and social functioning. At 18 months, the improvement in the role-physical score was significantly greater in the high-dose cyclophosphamide trial arm than in the monthly-dose cyclophosphamide arm (P = 0.025). At the end of the two and a half-year study, there were no significant differences between the groups with respect to changes in SF-36. By pooling the groups, at 30 months, there was a statistically significant (P < 0.05) improvement over baseline in 6 of the 8 SF-36 domains. This study shows earlier improvement in SF-36 measures at 6 months in the high-dose cyclophosphamide group but equal improvement in both arms at two and one and a half years. Eventual improvements in quality-of-life with both cyclophosphamide regimens are clinically meaningful to both patients and treating physicians.

Predictors of high sensitivity C-reactive protein levels in patients with systemic lupus erythematosus.

Despite the increased prevalence of cardiovascular disease in patients with systemic lupus erythematosus (SLE), little is known about the role of high sensitivity C-reactive protein (hsCRP) or whether ethnicity, gender, anthropometric measures and treatment can alter hsCRP levels. We evaluated the effects of treatment and demographic, anthropometric and socio-economic variables on hsCRP levels in SLE. High sensitivity C-reactive protein levels were measured using an immunoturbidimetric assay in 610 patients from the Hopkins Lupus Cohort, who were followed-up regularly. In stepwise multiple regression analyses, body mass index (BMI) [odds ratio (OR) 1.72, 95% confidence interval (CI) 1.34-2.20, P < 0.001], African-American ethnicity (OR 1.97, 95% CI 1.22-3.19, P < 0.01), education (OR 0.60, 95% CI 0.42-0.86, P < 0.01), statin use (OR 0.38, 95% CI 0.18-0.82, P < 0.05), estrogen use (OR 3.65, 95% CI 1.19-11.22, P < 0.05), SLE Disease Activity Index score (OR 1.76, 95% CI 1.09-2.87, P < 0.05) and cumulative prednisone dose (OR 1.27, 95% CI 1.01-1.60, P < 0.05) were significant predictors of hsCRP levels. These findings suggest that hsCRP levels should be adjusted for BMI, ethnicity, education level, disease activity and medications when conducting cardiovascular risk assessment in patients with lupus.