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.

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.

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.

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.

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.

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.

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.

Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases.

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.

Estimating renal function in lupus nephritis: comparison of the Modification of Diet in Renal Disease and Cockcroft Gault equations.

Estimates of renal function are widely used in clinical practice and research. We assessed the performance of the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) equations in lupus nephritis patients. Data from ninety-seven lupus nephritis patients in the Hopkins Lupus Cohort were reviewed. Two renal function estimates, the CG and the MDRD, were compared with the 24 h creatinine clearance (CrCl). In the entire group of patients, the CG and MDRD equations had good global agreement with CrCl (R-square = 0.91 and 0.69, respectively). On average the CG equation overestimated CrCl by 2.36 mL/min/1.73 m(2), whereas the MDRD equation underestimated CrCl by 5.85 mL/min/1.73 m(2), P = 0.0004. The CG equation had greater accuracy (mean squared error) than the MDRD equation (14.93 versus 28.47 mL/min/1.73 m(2), P = 0.002) when predicting CrCl. Although both equations lacked precision (standard deviation of the difference scores) in patients with CrCl > or = 60 mL/min/1.73 m(2), the CG equation was more precise than the MDRD equation in this group, (15.68 versus 29.58 mL/min/1.73 m(2), P = 0.003). In lupus nephritis patients, the CG equation was superior to the MDRD equation as an estimate of CrCl. However, both equations lacked precision in patients with CrCl > or = 60 mL/min/1.73 m(2).

Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis.

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P = 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P = 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.

Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results.

BACKGROUND/AIMS: A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications of chronic hepatitis C virus infection has not been done. SUBJECTS: One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements. METHODS: Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects. RESULTS: At 12 months almost all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months. CONCLUSIONS: The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.

Head growth and neurodevelopment of infants born to HIV-1-infected drug-using women.

OBJECTIVE: To describe neurodevelopment and head growth in HIV-1-infected and exposed uninfected infants with and without in utero exposure to opiates and cocaine. METHODS: Using data from a multicenter cohort study of HIV-1-infected women and their children, the authors fit repeated measures regression models to estimate the effects of HIV-1 infection and in utero hard drug exposure on head circumference and Bayley Scales of Infant Development standard scores during the first 30 months. RESULTS: Of the 1,094 infants included in the analysis, 147 (13%) were HIV-1-positive and 383 (35%) were exposed in utero to opiates or cocaine (drug-positive). Mean 4- month Bayley mental scores were lower in infants with only HIV-1 positivity (HIV-positive and drug-negative) (-8.2 points, p < 0.0001) or only drug exposure (HIV-negative and drug-positive) (-4.4 points, p = 0.0001) and tended to be lower in infants with both factors (HIV-positive and drug-positive) (-3.7 points, p = 0.0596), compared with those who were HIV-1-negative and not drug exposed (HIV-negative and drug-negative). However, by 24 months of age, there was no longer a decrement among HIV-negative and drug-positive infants, whereas HIV-1 infection was still associated with a decrement relative to uninfected infants. Similar results were seen for Bayley motor scores and for head circumference Z scores. CONCLUSIONS: HIV-1 infection and in utero opiate and cocaine exposure decrease birth head circumference and slow neurodevelopment at 4 months. At 24 months of age, however, only HIV-1 infection is associated with decreased neurodevelopment and head circumference. There may be some postnatal recovery from the effects of in utero hard drug exposure. Importantly, the detrimental effects of HIV-1 positivity and maternal hard drug use on neurodevelopment at 4 months are not additive, although they are additive for birth head circumference.

Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the degree to which changes in anti-double-stranded DNA (anti-dsDNA), as determined by Crithidia and enzyme-linked immunosorbent assays (ELISAs), precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 clinical indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG). METHODS: Disease activity and anti-dsDNA were measured monthly in 53 SLE patients who were followed up for 1 year. Lupus flare was defined as an increase in PGA of > or = 1.0, M-SLEDAI > or = 3, M-LAI > or = 0.1, SLAM > or = 3, and M-BILAG > or = 4 within a 1-month period. Flare rates were calculated for groups, which were defined by "previous" (1 month prior to the flare) or "concurrent" (at the time of the flare) changes in anti-dsDNA. Logistic regression models were used to determine the significance of the association between recent changes in anti-dsDNA and flare, controlling for the prednisone dosage. RESULTS: Flares occurred at 12% of visits, based on the PGA measure of disease activity. Using the other indices, flare rates were 19% (M-SLEDAI), 25% (M-LAI), 13% (SLAM), and 12% (M-BILAG). A concurrent decrease in anti-dsDNA (ELISA) was associated with significantly higher flare rates based on PGA (18 of 84, 21%; P = 0.0014), M-SLEDAI (27 of 89, 30%; P = 0.0019), M-LAI (37 of 89, 42%; P = 0.0001), and M-BILAG (19 of 89, 21%; P = 0.0264) scores. Flare rates were also significantly higher after a previous increase in anti-dsDNA (ELISA) based on M-SLEDAI (26 of 93, 30%; P = 0.0022) and M-LAI (34 of 93, 37%; P = 0.0117) scores. Flare rates tended to be lowest when there was a concurrent increase in anti-dsDNA (ELISA). Analysis of specific organ systems showed that a concurrent decrease in anti-dsDNA (ELISA) was significantly associated with increases in renal disease activity. Similar results were obtained using the Crithidia assay. CONCLUSION: A previous increase in anti-dsDNA levels occurred before SLE flares, as measured by the M-SLEDAI and M-LAI only. However, during lupus flares, including the subset of renal flares, anti-dsDNA levels frequently decreased. We hypothesize that this decrease in anti-dsDNA represents deposition in tissue at the time of flare.