Community-Engaged Research: Leveraging Community-Academic Partnerships to Reduce Disparities and Inequities in Lupus Care.

Community-engaged research is an effective tool to address health care disparities and inequities in lupus care. Community-based participatory research allows the highest degree of community engagement, but may be limited by the challenges associated with long-term funding and implementation. Community-academic partnerships are a feasible way to allow for varying degrees of community engagement and develop sustainable infrastructure. Two examples of community-engaged research in rheumatology are MONARCAS and Lupus Conversations.

Patient experiences and strategies for coping with SLE: A qualitative study.

OBJECTIVE: This study explored challenges that patients with systemic lupus erythematosus (SLE) and childhood-onset SLE (cSLE) face to identify modifiable influences and coping strategies in patient experiences. METHODS: Participants were recruited from two academic medical centers through a Lupus Registry of individuals ≥18 years old and ≥4 1997 ACR classification criteria for SLE and a centralized data repository of cSLE patients, and participated in three focus groups. Transcripts were coded thematically and adjudicated by two independent reviewers. RESULTS: Thirteen adults, 7 (54%) with cSLE, participated in focus groups. Themes were categorized into two domains: (1) challenges with SLE diagnosis and management; and (2) patient coping strategies and modifiable factors of the SLE experience. Participants identified five primary challenges: diagnostic odyssey, public versus private face of SLE, SLE-related stresses, medication adherence, and transitioning from pediatric to adult care. Coping strategies and modifiable factors included social support, open communication about SLE, and strong patient-provider relationships. Several participants highlighted positive lessons learned through their experiences with SLE, including empathy, resilience, and self-care skills. CONCLUSIONS: Patients with cSLE and SLE identified common challenges, modifying influences and coping strategies based on personal experiences. A strong patient-provider relationship and trust in the medical team emerged as key modifiable factors. Deriving optimism from experiences with SLE was unique to several patients diagnosed as children or young adults. Leveraging factors that improved the participants' experiences living with SLE may be used in future studies to address vulnerabilities in care.

Treat-to-Target Approach in Rheumatoid Arthritis: A Quality Improvement Trial.

OBJECTIVE: Using a quality improvement approach, our objective was to integrate a treat-to-target approach for rheumatoid arthritis (RA) through routine electronic collection of patient-reported disease activity scores and a multidisciplinary learning collaborative for rheumatologists. METHODS: RA patients completed a patient-reported outcome measure, the Routine Assessment of Patient Index Data 3 (RAPID3), at check-in. Nine rheumatologists and their patients were allocated to a learning collaborative intervention group focused on a treat-to-target approach and 13 were allocated to a control group. The primary outcome was documentation of a treat-to-target implementation score: disease activity score, disease activity score used in the medication change decision, the presence of a treatment target, and an indication of shared decision-making. A primary analysis of patient visits with medication changes was conducted using an interrupted time-series analysis. RESULTS: We studied 554 individual rheumatology patients with 709 patient visits. Treat-to-target implementation scores among intervention rheumatologists (mean ± SD 44.6% ± 1.63%) were 12.4% higher than in the control group (mean ± SD 32.2% ± 1.50%; P < 0.0001). We observed differences in treat-to-target implementation score components, comparing intervention group to control group rheumatologists: disease activity score present, 77.2% versus 68.0% (P = 0.02); disease activity score used in the medication change decision, 45.2% versus 30.0% (P < 0.01); treatment target, 9.0% versus 0.4% (P < 0.01); and shared decision-making, 46.9% versus 30.0% (P < 0.01). Secondary analysis of patient visits with high RAPID3 scores found that medication changes were 54% less likely in the intervention versus control group (odds ratio 0.46 [95% confidence interval 0.27-0.79], P = 0.005). CONCLUSION: This nonrandomized, interrupted time-series trial demonstrated a modest but significant impact of a learning collaborative intervention on rheumatologist documentation of a treat-to-target approach in RA.

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses' Health Study and Nurses' Health Study II.

OBJECTIVE: Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti-double-stranded DNA (anti-dsDNA) positive versus negative subtypes. METHODS: We studied 79,568 women in the Nurses' Health Study (1984-2014) and 93,554 in the Nurses' Health Study II (1991-2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI-2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time-varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti-dsDNA, for cumulative average dietary quality score tertiles and individual AHEI-2010 components. RESULTS: We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI-2010 HR 0.78 [95% CI 0.54-1.14], aMed HR 0.82 [95% CI 0.56-1.18], DASH HR 1.16 [95% CI 0.81-1.66], EDIP HR 0.83 [95% CI 0.57-1.21]). No association was demonstrated for anti-dsDNA+ or anti-dsDNA- SLE risk. Women in the highest (versus lowest) AHEI-2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40-0.87]). No association was demonstrated for other AHEI-2010 components and SLE risk. CONCLUSION: We observed no association between long-term adherence to the AHEI-2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation.

Association of Child Abuse and Systemic Lupus Erythematosus in Black Women During Adulthood.

OBJECTIVE: Exposure to psychosocial stressors may contribute to the onset of systemic lupus erythematosus (SLE) through dysregulation of the adaptive stress response. The present study was undertaken to assess the relationship of childhood physical and sexual abuse to risk of SLE among Black women. METHODS: Using data from the Black Women's Health Study, we followed 36,152 women from 1995 through 2015 with biennial questionnaires. Women reported on exposure to abuse during childhood (up to age 11) in 2005. Self-reported cases of incident SLE were confirmed as meeting the American College of Rheumatology SLE classification criteria by medical record review. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for SLE among women exposed to physical or sexual abuse during childhood, controlling for potential confounders. RESULTS: We confirmed 101 cases of incident SLE and identified patients who had completed questions on child abuse during 670,822 person-years of follow-up. Both physical and sexual abuse during childhood were associated with statistically significant increases in SLE incidence. The HR for SLE associated with ≥2 episodes of severe sexual abuse compared to no abuse was 2.51 (95% CI 1.29-4.85) after adjustment for alcohol consumption, smoking, body mass index, oral contraceptive use, age at menarche, and parental education. The multivariable-adjusted HR for SLE with ≥5 episodes of severe physical abuse was 2.37 (95% CI 1.13-4.99). CONCLUSION: Our results suggest that sexual and physical abuse during childhood increase SLE risk during adulthood among Black women. Research is necessary both to confirm this finding and to understand potential mediating mechanisms.

Associations Between Smoking and Systemic Lupus Erythematosus-Related Cytokines and Chemokines Among US Female Nurses.

OBJECTIVE: Smoking has been associated with increased systemic lupus erythematosus (SLE) risk, but the biologic basis for this association is unknown. Our objective was to investigate whether women's smoking was positively associated with SLE-associated proinflammatory chemokines/cytokines (stem cell factor [SCF], B lymphocyte stimulator [BLyS], interferon-γ-inducible 10-kd protein [IP-10], and interferon-α); or negatively associated with antiinflammatory cytokine interleukin-10 (IL-10); and whether associations were modified by SLE-related autoantibody status. METHODS: The Nurses' Health Study (NHS, n = 121,700) and NHSII (n = 116,429) cohorts were begun in 1976 and 1989. In 1988-1990 (NHS) and 1996-1999 (NHSII), ~25% of participants donated blood samples. We identified 1,177 women without SLE with banked samples, and we tested by enzyme-linked immunoassay (ELISA) for chemokines/cytokines as well as anti-Sm, anti-Ro/SSA, anti-La/SSB, and anti-RNP. Antinuclear antibodies (ANAs) were detected by HEp-2 cell indirect immunofluorescence, and anti-double-stranded DNA antibodies and were assayed by ELISA. Smoking was assessed until blood draw. Separate tobit and linear regression analyses, adjusted for potential confounders, modeled associations between smoking and log-transformed chemokine/cytokine concentrations. Analyses were stratified by autoantibody status. Effect estimates were calculated as ratios of geometric means expressed as percentage differences. RESULTS: Among the 15% of current/recent versus 85% of past/never smokers, BLyS levels were 8.7% higher (P < 0.01) and were 24% higher (P < 0.0001) among those who were ANA positive. Current/recent smokers had IL-10 concentrations 46% lower (P < 0.01) than past/never smokers; each 10 pack-years of smoking was associated with a 17% decrease in IL-10 level (P < 0.001). Smoking was not associated with IP-10 or SCF. CONCLUSION: Elevated BLyS and lower IL-10 levels among current smokers, particularly among ANA-positive women, may be involved in SLE pathogenesis.

Associations between daily alcohol consumption and systemic lupus erythematosus-related cytokines and chemokines among US female nurses without SLE.

OBJECTIVES: Moderate alcohol consumption has been associated with decreased systemic lupus erythematosus risk, but the biologic basis for this association is unknown. We aimed to determine whether moderate alcohol consumption was associated with lower concentrations of systemic lupus erythematosus-associated chemokines/cytokines in an ongoing cohort of female nurses without systemic lupus erythematosus, and whether the association was modified by the presence of systemic lupus erythematosus-related autoantibodies. METHODS: About 25% of participants from the Nurses' Health Study (n = 121,700 women) and Nurses' Health Study 2 (n = 116,429) donated a blood sample; of these, 1177 women were without systemic lupus erythematosus at time of donation. Cumulative average and current (within 4 years) intakes of beer, wine or liquor were assessed from pre-blood draw questionnaires. Chemokine/cytokine concentrations (stem cell factor, B-lymphocyte stimulator, interferon-inducible protein-10, interferon-alpha, interleukin-10) and antibodies against dsDNA and extractable nuclear antigens were obtained using enzyme-linked immunosorbent assays. Antinuclear antibodies were detected by indirect immunofluorescence on HEp-2 cells. RESULTS: At blood draw, the women's mean age was 56 years and 22% were antinuclear antibody positive; 36% were African-American. About half (46%) reported consuming 0-5 g/day of alcohol. Stem cell factor levels were 0.5% lower (p < 0.0001) for every gram per day increase in cumulative average alcohol consumption. Women who consumed >5 g/day had mean stem cell factor levels 7% lower (p = 0.002) than non-drinkers. Other cytokines were not significantly associated with alcohol intake. Autoantibody status did not modify observed associations. CONCLUSION: In this study of female nurses, moderate alcohol consumption was associated with lower stem cell factor levels, suggesting a plausible mechanism through which alcohol may lower systemic lupus erythematosus risk might be by decreasing circulating stem cell factor.

Renal deposits of complement factors as predictors of end-stage renal disease and death in patients with lupus nephritis.

OBJECTIVE: Lupus nephritis (LN) increases the risks of end-stage renal disease (ESRD) and death, but these risks are difficult to estimate. Since complement factors play an essential role in the pathogenesis and are deposited in the kidneys as C1q and C3, we studied whether these deposits predict ESRD and death in patients with LN. METHODS: We collected demographic, clinical and pathological data from 183 adult patients with LN classes II-V diagnosed with a first native kidney biopsy. Pathological data included the localization and intensity of immunofluorescence staining of C1q and C3. We obtained dates of incident ESRD and death from the United States Renal Data System and National Death Index, respectively, and evaluated survival curves and hazard ratios for ESRD and death as a composite outcome and as separate outcomes. RESULTS: The presence and intensity of deposits of C1q and C3 in glomeruli, tubular walls and vascular walls differed between classes and were associated with known unfavourable prognostic factors, such as hypertension, hypoalbuminemia and hypocomplementemia. However, over a median follow-up of 7.5 years, their presence and intensity were associated with neither survival free of ESRD and death nor hazard ratios for ESRD and death. CONCLUSION: Renal deposits of complement factors did not predict ESRD and death in patients with LN.

Quality improvement for rheumatoid arthritis care: results from a focus group.

OBJECTIVES: Complex treatment decisions in rheumatoid arthritis (RA) affect aspects of patients' physical, psychological and emotional well-being. We aimed to identify key attributes of patient-centered rheumatologic care for adults with RA through a qualitative study using patient focus group discussions in order to guide quality improvement efforts around optimisation of disease management. METHODS: Patients with RA were recruited from a large academic medical centre rheumatology clinic and its affiliate sites over one month and allocated into focus groups led by an experienced moderator. Focus groups were held until thematic saturation was reached. Patients' responses were examined, categorised into themes, and codified independently by three reviewers. We extracted statements identifying common themes from transcripts. RESULTS: Thirteen patients with RA were recruited and allocated into three focus groups. Mean age was 59.1±10.1 years and average RA disease duration was 17.8 years. All participants had experience taking at least one disease-modifying anti-rheumatic drug (DMARD). Following reviewer analysis of patients' responses, six common themes about quality RA care were identified including: the role and use of self-management strategies, the clinical environment, the health care delivery process, attitudes towards medication, insurance and medication access issues, and the impact of disease on lifestyle. CONCLUSIONS: Themes uncovered in focus group discussions related predominantly to the clinical environment and patient-provider communication. These preliminary results identified the need to incorporate operational aspects of health care delivery into our assessment of the RA patient experience and formed the basis of a RA quality improvement programme targeting medication optimisation.

Clinical characteristics and renal prognosis associated with interstitial fibrosis and tubular atrophy (IFTA) and vascular injury in lupus nephritis biopsies.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) and vascular injury are frequent histologic features of lupus nephritis renal biopsies, but their clinical correlates and prognostic value are not well understood. This cohort study investigated demographic, clinical and laboratory characteristics, and outcomes, associated with IFTA and vascular injury in lupus nephritis. METHODS: Reports of all renal biopsies performed at an academic medical center (1990-2017) with WHO/ISN/RPS Class II-V lupus nephritis were reviewed. Demographics, clinical variables and labs at biopsy, treatment, and date of death were collected. Additional data from the U.S. Renal Data System (USRDS) provided dates of ESRD and death after ESRD. Multivariable regression analyses identified demographic and clinical factors associated with each histologic finding. Cumulative incidence functions and multivariable Cox proportional hazard models estimated the risk of progression to ESRD and death. RESULTS: Within 202 initial biopsies, IFTA was associated with the patient's SLICC/ACR damage index (without renal domain) and serum creatinine, and vascular injury was associated with serum creatinine in multivariable models. In Cox regression models adjusting for age, sex, race, serum creatinine, calendar year, and biopsy class, moderate/severe IFTA was associated with elevated ESRD (HRSD 5.18, 95% CI 2.53, 10.59) and death (HR 4.19, 95%CI 1.27, 13.81). After adjustment for age, sex and race, moderate/severe vascular injury was associated with ESRD (HRSD 2.13, 95% CI 1.21, 3.75) and but this relationship was not significant after adjustment for serum creatinine and calendar year. CONCLUSIONS: IFTA is a strong predictor of ESRD and death, even in proliferative nephritis, and a risk factor for poor outcomes independent of class. Vascular injury is a strong predictor of prognosis, but not independent of serum creatinine and class. The prognostic value of these lesions calls for consideration when determining treatment for lupus nephritis.

Association of Childhood Abuse with Incident Systemic Lupus Erythematosus in Adulthood in a Longitudinal Cohort of Women.

OBJECTIVE: Exposure to severe stressors may alter immune function and augment inflammation and cytokine release, increasing risk of autoimmune disease. We examined whether childhood abuse was associated with a heightened risk of incident systemic lupus erythematosus (SLE). METHODS: Data were drawn from the Nurses' Health Study II, a cohort of US female nurses enrolled in 1989, followed with biennial questionnaires. We measured childhood physical and emotional abuse with the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and sexual abuse with the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale, both administered in 2001. We identified incident SLE (≥ 4 American College of Rheumatology 1997 classification criteria) through 2015. We used multivariable Cox regression models to evaluate the association between childhood abuse and SLE, accounting for potential confounders (e.g., parental education, occupation, home ownership) and mediators [e.g., depression, posttraumatic stress disorder (PTSD)]. RESULTS: Among 67,516 women, there were 94 cases of incident SLE. In adjusted models, exposure to the highest versus lowest physical and emotional abuse was associated with 2.57 times greater risk of SLE (95% CI 1.30-5.12). We found that 17% (p < 0.0001) of SLE risk associated with abuse could be explained by depression and 23% (p < 0.0001) by PTSD. We did not observe a statistically significant association with sexual abuse (HR 0.84, 95% CI 0.40-1.77, highest vs lowest exposure). CONCLUSION: We observed significantly increased risk of SLE among women who had experienced childhood physical and emotional abuse compared with women who had not. Exposure to childhood adversity may contribute to development of SLE.

Impact and Timing of Smoking Cessation on Reducing Risk of Rheumatoid Arthritis Among Women in the Nurses' Health Studies.

OBJECTIVE: To investigate the impact and timing of smoking cessation on developing rheumatoid arthritis (RA) and serologic phenotypes. METHODS: We investigated smoking cessation and RA risk in the Nurses' Health Study (NHS) (1976-2014) and the NHS II (1989-2015). Smoking exposures and covariates were obtained by biennial questionnaires. Self-reported RA was confirmed by medical record review for American College of Rheumatology/European League Against Rheumatism criteria. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RA serologic phenotypes (all, seropositive, seronegative) according to smoking status, intensity, pack-years, and years since cessation. RESULTS: Among 230,732 women, we identified 1,528 incident cases of RA (63.4% of which were seropositive) during 6,037,151 person-years of follow-up. Compared with never smoking, current smoking increased the risk of all RA (multivariable HR 1.47, 95% CI 1.27-1.72) and seropositive RA (HR 1.67, 95% CI 1.38-2.01) but not seronegative RA (HR 1.20, 95% CI 0.93-1.55). An increasing number of smoking pack-years was associated with an increased trend for the risk of all RA (P < 0.0001) and seropositive RA (P < 0.0001). With increasing duration of smoking cessation, a decreased trend for the risk of all RA was observed (P = 0.009) and seropositive RA (P = 0.002). Compared to recent quitters (<5 years), those who quit ≥30 years ago had an HR of 0.63 (95% CI 0.44-0.90) for seropositive RA. However, a modestly increased risk of RA was still detectable 30 years after quitting smoking (for all RA, HR 1.25 [95% CI 1.02-1.53]; for seropositive RA, HR 1.30 [95% CI 1.01-1.68]; reference, never smoking). CONCLUSION: These results confirm that smoking is a strong risk factor for developing seropositive RA and demonstrate for the first time that a behavior change of sustained smoking cessation could delay or even prevent seropositive RA.

Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women.

Our objective was to investigate whether a dietary pattern derived using inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. We prospectively followed 79,988 women in the Nurses' Health Study (NHS, 1984-2014) and 93,572 women in the NHSII (1991-2013); incident RA was confirmed by medical records. Food frequency questionnaires (FFQ) were completed at baseline and approximately every 4 years. Inflammatory dietary pattern was assessed from FFQ data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti-/pro-inflammatory food/beverage groups weighted by correlations with plasma inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis factor-α receptor 2). We investigated associations between EDIP and RA using Cox regression. We identified 1185 incident RA cases over 4,425,434 person-years. EDIP was not associated with overall RA risk (p trend = 0.21 across EDIP quartiles). Among women ≤ 55 years, increasing EDIP was associated with increased overall RA risk; HRs (95% CIs) across EDIP quartiles were 1.00 (reference), 1.14 (0.86-1.51), 1.35 (1.03-1.77), and 1.38 (1.05-1.83; p for trend = 0.01). Adjusting for BMI attenuated this association. Increasing EDIP was associated with increased seropositive RA risk among women ≤ 55 years (p for trend = 0.04). There was no association between EDIP and RA among women > 55 years (EDIP-age interaction, p = 0.03). An inflammatory dietary pattern was associated with increased seropositive RA risk with onset ≤ 55 years old, and this association may be partially mediated through BMI.

Relationship of Cigarette Smoking and Alcohol Consumption to Incidence of Systemic Lupus Erythematosus in a Prospective Cohort Study of Black Women.

OBJECTIVE: Systemic lupus erythematosus (SLE) affects black women more frequently than other racial/gender groups. In past studies, largely consisting of white and Asian cohorts, cigarette smoking was associated with increased SLE risk, and moderate alcohol consumption was associated with decreased SLE risk. The aim of this study was to assess associations of smoking and alcohol consumption with the risk of incident SLE among black women, using data from a long-term, prospective, follow-up study. METHODS: The Black Women's Health Study enrolled 59,000 black women in 1995 and collected data on demographics, health status, and medical and lifestyle variables. Follow-up questionnaires that were given every 2 years identified incident disease and updated risk factors. Cases of incident SLE that met the American College of Rheumatology revised criteria for SLE as updated in 1997 were confirmed through medical record review. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for associations of cigarette smoking and alcohol intake with incidence of SLE. RESULTS: A total of 127 incident SLE cases from 1995 to 2015 (mean age 43 years at diagnosis) were confirmed. Compared to never smokers, the risk of SLE among ever smokers was elevated, but not significantly (HR 1.45 [95% CI 0.97-2.18]). Risk was similar for current and past smoking and increased nonsignificantly with increasing pack-years. The HR was 0.71 (95% CI 0.45-1.12) for current drinking relative to never drinking, with a HR of 0.43 (95% CI 0.19-0.96) for ≥4 drinks/week. CONCLUSION: Findings from this large study of SLE risk among black women are consistent with previous results from studies in other populations of increased risk of SLE associated with cigarette smoking and decreased risk with moderate alcohol consumption.

A prospective study of obesity and risk of systemic lupus erythematosus (SLE) among Black women.

BACKGROUND: Obesity may influence systemic lupus erythematous (SLE) pathogenesis via stimulation of systemic inflammation, but the relationship between obesity and SLE risk is unclear. Past studies have predominantly assessed White women, while Black women have higher prevalence of both obesity and SLE. METHODS: We prospectively assessed the relationship between Body Mass Index (BMI, kg/m2) and incident SLE within the Black Women's Health Study (median age 38 at entry in 1995). Height and weight at age 18 and during follow-up were self-reported. We confirmed incident SLE cases by updated American College of Rheumatology criteria and collected covariates prospectively. Cox proportional hazards regression models, adjusted for potential confounders, estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for categories of updated BMI and risk of SLE, relative to BMI 20-24.9 ("normal" BMI). Secondary analyses investigated BMI at age 18, BMI in 1995 at cohort entry, cumulative updated BMI and "lagged" BMI (≥4 years prior to outcome window to address possible reverse causation). RESULTS: Adult obesity was not related to SLE risk: HR for BMI ≥30 ("obesity") relative to normal BMI at ≥4 years prior to SLE diagnosis was 0.90 (95% CI 0.53-1.54). However, obesity at age 18 was associated with increased risk: HR 2.38 (95% CI 1.26-4.51) for ≥30 vs. normal BMI. CONCLUSIONS: Among these Black women, obesity as a teenager was associated with increased SLE risk in adulthood. Further studies are necessary to understand the biologic mechanisms and windows of exposure for the relationship of obesity to SLE pathogenesis.

Challenging cases in rheumatic pregnancies.

This article describes three complicated cases in rheumatology and pregnancy. The first case elucidates the challenges in treating SLE in conjunction with pulmonary arterial hypertension, while the second case features an SLE-affected pregnancy with development of portal hypertension secondary to portal vein thrombosis related to APS. The third case is a pregnant woman with stable SLE who developed thrombotic microangiopathy caused by atypical haemolytic uraemic syndrome, and failed to improve despite multiple measures including biopsy and elective preterm delivery. There are grave and unique challenges for women with autoimmune disease, but adverse outcomes can sometimes be avoided with careful and multidisciplinary medical management. Pre-conception counselling with regard to medications and disease treatment should also include discussion of the advisability of pregnancy, which may be difficult for a patient, but present the best course for optimizing health outcomes.

Did King Herod suffer from a rheumatic disease?

Herod the Great was appointed "king of Jews," to govern Judea, by the Roman Emperor and Senate. He lived from 73/74 BCE to 4 CE. He died with an illness and symptoms that have been the source of considerable speculation. Richard Strauss depicted Herod in his classic opera, "Salome." That opera was derived from a play of the same name by Oscar Wilde, which was based on an 1876 painting, "Salome Dancing Before Herod," by Gustave Moreau. The operatic Herod was afflicted with an illness characterized by dementia, hallucinations, paranoia, alcoholism (from drinking the Emperor's wine), violence, twitches, and sterility; different interpretations showed him also with falls, chills, shaking, thirst, forgetfulness, and sleepiness, for which we suggest the novel diagnosis of chronic lead intoxication (which can manifest to rheumatologists as saturnine gout). He had compatible symptoms (encephalopathy and neuromuscular abnormalities) and consumed excessive quantities of imperial wine, known to be highly contaminated with lead and likely associated with similar symptoms among Roman aristocracy. Herod's demented cruelties-an oppressive reign which including the beheading of John the Baptist-exacerbated the political climate and may have contributed to the subsequent violent 7-year revolt culminating in the destruction of the second temple. How different might history have been if Herod the Great had been abstemious?

Developmental programming by maternal insulin resistance: hyperinsulinemia, glucose intolerance, and dysregulated lipid metabolism in male offspring of insulin-resistant mice.

Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.

A low-literacy medication education tool for safety-net hospital patients.

BACKGROUND: To improve medication adherence in cardiac patients, in partnership with a safety-net provider, this research team developed and evaluated a low-literacy medication education tool. METHODS: Using principles of community-based participatory research, the team developed a prototype of a low-literacy hospital discharge medication education tool, customizable for each patient, featuring instruction-specific icons and pictures of pills. In 2007, a randomized controlled clinical trial was performed, testing the tool's effect on posthospitalization self-reported medication adherence and knowledge, 2 weeks postdischarge in English- and Spanish-speaking safety-net inpatients. To validate the self-report measure, 4 weeks postdischarge, investigators collected self-reports of the number of pills remaining for each medication in a subsample of participants. Nurses rated tool acceptability. RESULTS: Among the 166/210 eligible participants (79%) completing the Week-2 interview, self-reported medication adherence was 70% (95% CI=62%, 79%) in intervention participants and 78% (95% CI=72%, 84%) in controls (p=0.13). Among the 85 participants (31%) completing the Week-4 interview, self-reported pill counts indicated high adherence (greater than 90%) and did not differ between study arms. Self-reported adherence was correlated with self-reported pill count in intervention participants (R=0.5, p=0.004) but not in controls (R=0.07, p=0.65). There were no differences by study arm in medication knowledge. The nurses rated the tool as highly acceptable. CONCLUSIONS: Although the evaluation did not demonstrate the tool to have any effect on self-reported medication adherence, patients who received the schedule self-reported their medication adherence more accurately, perhaps indicating improved understanding of their medication regimen and awareness of non-adherence.