Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities.

OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. METHODS: Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. RESULTS: Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. CONCLUSION: The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities.

B cell subset composition segments clinically and serologically distinct groups in chronic cutaneous lupus erythematosus.

OBJECTIVE: While the contribution of B-cells to SLE is well established, its role in chronic cutaneous lupus erythematosus (CCLE) remains unclear. Here, we compare B-cell and serum auto-antibody profiles between patients with systemic lupus erythematosus (SLE), CCLE, and overlap conditions. METHODS: B-cells were compared by flow cytometry amongst healthy controls, CCLE without systemic lupus (CCLE+/SLE-) and SLE patients with (SLE+/CCLE+) or without CCLE (SLE+/CCLE-). Serum was analyed for autoreactive 9G4+, anti-double-stranded DNA, anti-chromatin and anti-RNA antibodies by ELISA and for anti-RNA binding proteins (RBP) by luciferase immunoprecipitation. RESULTS: Patients with CCLE+/SLE- share B-cell abnormalities with SLE including decreased unswitched memory and increased effector B-cells albeit at a lower level than SLE patients. Similarly, both SLE and CCLE+/SLE- patients have elevated 9G4+ IgG autoantibodies despite lower levels of anti-nucleic acid and anti-RBP antibodies in CCLE+/SLE-. CCLE+/SLE- patients could be stratified into those with SLE-like B-cell profiles and a separate group with normal B-cell profiles. The former group was more serologically active and more likely to have disseminated skin lesions. CONCLUSION: CCLE displays perturbations in B-cell homeostasis and partial B-cell tolerance breakdown. Our study demonstrates that this entity is immunologically heterogeneous and includes a disease segment whose B-cell compartment resembles SLE and is clinically associated with enhanced serological activity and more extensive skin disease. This picture suggests that SLE-like B-cell changes in primary CCLE may help identify patients at risk for subsequent development of SLE. B-cell profiling in CCLE might also indentify candidates who would benefit from B-cell targeted therapies.

Racial Disparities in Mortality Associated with Systemic Lupus Erythematosus - Fulton and DeKalb Counties, Georgia, 2002-2016.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with often nonspecific symptoms that can lead to a delay in diagnosis. The disease disproportionately affects women and minorities. Blacks with SLE also have more severe disease and develop it at an earlier age (1). Despite an increase in the 5-year survival rate from 50% in 1955 to approximately 90% in the 2000s, attributed largely to advances in management of SLE (2), premature mortality among SLE patients persists, often as a result of disease severity, infections, and cardiovascular disease. Because existing SLE mortality estimates based on death certificate data are known to underestimate SLE deaths (3), SLE mortality was analyzed using 2002-2004 data from the population-based Georgia Lupus Registry (1). Incident and prevalent SLE cases matched to the National Death Index through 2016 identified 97 and 401 deaths, respectively. Standardized mortality ratios adjusted for age group, sex, and race were two to three times higher among persons with SLE relative to expected deaths in the general population. Blacks had significantly higher cumulative mortality than did whites, and blacks with both incident and prevalent cases were significantly younger at death (mean age 51.8 and 52.3 years, respectively) than were whites (mean age 64.4 and 65.0 years, respectively). Whites had lower mortality after diagnosis than did blacks; among incident cases, mortality among whites did not occur until 5 years after SLE diagnosis, whereas blacks had significantly and persistently higher mortality from the time of diagnosis. There were no significant differences by sex. Current CDC-supported efforts encourage early detection, diagnosis, and treatment, and enhanced self-management skills to mitigate racial disparities and improve outcomes overall among persons with SLE.

Replicative DNA polymerase δ but not ε proofreads errors in Cis and in Trans.

It is now well established that in yeast, and likely most eukaryotic organisms, initial DNA replication of the leading strand is by DNA polymerase ε and of the lagging strand by DNA polymerase δ. However, the role of Pol δ in replication of the leading strand is uncertain. In this work, we use a reporter system in Saccharomyces cerevisiae to measure mutation rates at specific base pairs in order to determine the effect of heterozygous or homozygous proofreading-defective mutants of either Pol ε or Pol δ in diploid strains. We find that wild-type Pol ε molecules cannot proofread errors created by proofreading-defective Pol ε molecules, whereas Pol δ can not only proofread errors created by proofreading-defective Pol δ molecules, but can also proofread errors created by Pol ε-defective molecules. These results suggest that any interruption in DNA synthesis on the leading strand is likely to result in completion by Pol δ and also explain the higher mutation rates observed in Pol δ-proofreading mutants compared to Pol ε-proofreading defective mutants. For strains reverting via AT→GC, TA→GC, CG→AT, and GC→AT mutations, we find in addition a strong effect of gene orientation on mutation rate in proofreading-defective strains and demonstrate that much of this orientation dependence is due to differential efficiencies of mispair elongation. We also find that a 3'-terminal 8 oxoG, unlike a 3'-terminal G, is efficiently extended opposite an A and is not subject to proofreading. Proofreading mutations have been shown to result in tumor formation in both mice and humans; the results presented here can help explain the properties exhibited by those proofreading mutants.

Depressive Symptoms Are Associated With Low Treatment Adherence in African American Individuals With Systemic Lupus Erythematosus.

OBJECTIVE: African American (AA) people with systemic lupus erythematosus (SLE) are at high morbidity and mortality risk, and they often require multiple medications. Low medication adherence is a highly prevalent, multidimensional problem associated with poor outcomes in people with SLE. Depression, a predictor of low adherence in people with chronic conditions, has been described in over 35% of AAs with SLE. We hypothesized that depressive symptoms would be increasingly associated with low adherence in this population. METHODS: Research subjects predominantly belong to the Georgians Organized Against Lupus cohort, a population-based cohort of predominantly AA individuals with SLE in the Atlanta metropolitan area. Medication adherence and severity of depressive symptoms were measured using validated self-reported tools: the 8-item Morisky Medication Adherence Scale and the 9-item Patient Health Questionnaire, respectively. We used univariate and multivariate logistic regression to examine the odds ratios of low medication adherence across individuals with increasing severity of depressive symptoms. RESULTS: Among 632 AA SLE participants, 336 (54%) reported low medication adherence and 217 (34.6%) reported "moderate" or "severe" depressive symptoms. In univariate logistic regression, significant risk factors for low adherence were depressive symptoms, low self-efficacy, poor satisfaction with care, female sex, younger age, hurried patient-physician communication, poorer shared decision-making, less compassionate physician communication style, poor/fair health, and higher disease activity score. In multivariate regression, younger age, female sex, and more severe depressive symptoms were associated with low medication adherence. CONCLUSIONS: This is the first study to examine factors associated with low medication adherence among a population-based cohort of AA individuals with SLE. Depression was a strong correlate of low medication adherence. Mental health interventions aiming to address and treat depression may increase medication adherence.

Mismatch repair-dependent mutagenesis in nondividing cells.

Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.

Implementing a Staff-Led Smoking Cessation Intervention in a Diverse Safety-Net Rheumatology Clinic: A Pre-Post Scalability Study in a Low-Resource Setting.

OBJECTIVE: Quit Connect (QC), our specialty clinic smoking cessation intervention, supports clinic staff to check, advise, and connect willing patients to a state quit line or class. QC improved tobacco screening and quit line referrals 26-fold in a predominantly White academic health care system population. Implementing QC includes education, electronic health record (EHR) reminders, and periodic audit feedback. This study tested QC's feasibility and impact in a safety-net rheumatology clinic with a predominantly Black population. METHODS: In this pre-post study, adult rheumatology visits were analyzed 12 months before through 18 months after QC intervention (November 2019 through November 2021, omitting COVID-19 peak April through November 2020). EHR data compared process and clinical outcomes, including offers, referrals to resources, completed referrals, and documented cessation. Clinic staff engaged in pre-post focus groups and questionnaires regarding intervention feasibility and acceptability. Cost-effectiveness was also assessed. RESULTS: Visit-level patients who smoked were 89.8% Black and 69.5% women (n = 550). Before intervention, clinic staff rarely asked patients about readiness to cut back smoking (<10% assessment). After QC intervention, staff assessed quit readiness in 31.8% of visits with patients who smoked (vs 8.1% before); 58.9% of these patients endorsed readiness to cut back or quit. Of 102 accepting cessation services, 37% (n = 17) of those reached set a quit date. Staff found the intervention feasible and acceptable. Each quit attempt cost approximately $4 to $10. CONCLUSION: In a safety-net rheumatology clinic with a predominantly Black population, QC improved tobacco screening, readiness-to-quit assessment, and referrals and was also feasible and cost-effective.

Factors Associated With the Initiation and Retention of Patients With Lupus in the Chronic Disease Self-Management Program.

OBJECTIVE: The Chronic Disease Self-Management Program (CDSMP) is designed to enhance patients' self-efficacy and skills to manage their chronic illness. There is compelling evidence for the benefits of the CDSMP among patients with systemic lupus erythematosus (SLE); however, little is known about predictors of participation among Black women with SLE. We examined factors associated with CDSMP initiation and completion in this population. METHODS: We studied 228 Black women with SLE who consented to attend a CDSMP workshop. We used logistic regression to calculate unadjusted and adjusted odds ratios (ORs) for being a CDSMP initiator (a participant registered into the CDSMP who attended at least 1 of the first 2 weekly classes) and a CDSMP completer (a participant who completed at least 4 of 6 weekly classes). RESULTS: The majority of participants were CDSMP initiators (74% [n = 168]). Of those, 126 (75%) were CDSMP completers. Older age (adjusted OR [ORadj ] 1.03 [95% confidence interval (95% CI) 1.00-1.06]) and unemployment/disability (ORadj 2.05 [95% CI 1.05-4.14]) increased the odds of being a CDSMP initiator. The odds of initiating the CDSMP decreased by 22% for each additional child in the household (OR 0.78 [95% CI 0.62-0.98]), but this association became nonsignificant in the adjusted model (ORadj 0.89 [95% CI 0.68-1.18]). The only factor that differed significantly between CDSMP completers and noncompleters was age, with 4% higher odds of being a completer for each additional year of age (ORadj 1.04 [95% CI 1.00-1.07]). CONCLUSION: Our findings suggest that young Black women with SLE face barriers to attend and complete in-person CDSMP workshops, possibly in relation to work and child care demands.

Performance of Modified ALMS and BLISS Criteria with Standard of Care Treatment in Two US Health Care Systems.

OBJECTIVE: A retrospective cohort study was undertaken in a predominantly Black population undergoing standard treatment for lupus nephritis (LN) to estimate the incidence of, and risk factors for, complete response (CR) according to modified Aspreva Lupus Management Study (mALMS) and modified Belimumab International Study in Lupus Nephritis (mBLISS) criteria by 12 months. METHODS: Patients with biopsy-proven LN class III or IV ± V, urine protein-to-creatinine ratio of ≥1gm/gm and estimated glomerular filtration rate of >50 ml/minute/1.73 m2 at the time of the incident LN flare were included. The clinical, treatment, and laboratory factors associated with CR were identified using multivariable Cox regression. RESULTS: Of 173 patients, 86.1% were women, 77.5% were Black, and over half (59.5%) had non-commercial insurance. By 12 months, 20.6% (95% confidence interval (95% CI) 14.6-28.6%) achieved mALMS CR and 33.7% (95% CI 26.4-42.4%) achieved mBLISS CR. Factors associated with mBLISS CR were commercial insurance (adjusted CR ratio = 3.5 [95% CI 1.9-6.7]; P < 0.001), albumin (adjusted CR ratio = 1.8 per 1 gm/dl increase in albumin; P = 0.02), and low C4 (adjusted CR ratio = 2.6; P = 0.03). Cumulative incidence of end-stage renal disease (ESRD) at 3 years was 23.1% (95% CI 15.7-31.3%) and 6.1% (95% CI 2.8-11.1%) for death. Patients with non-commercial insurance were more likely to develop ESRD, with cumulative incidence of 30.4% (95% CI 19.6-41.9%) compared to 12.7% (95% CI 5.0-24.2%) for patients with commercial insurance (P = 0.024). CONCLUSION: In a primarily Black, uninsured LN population, despite achieving similar CR rates at 12 months, the incidence of ESRD and death exceeded those observed in controlled clinical trials with placebo arms.

Coagulopathy is prevalent and associated with adverse outcomes in transfused pediatric trauma patients.

OBJECTIVE: To evaluate coagulopathy in pediatric trauma patients on presentation to the emergency department, and to quantify the relationship with mortality. STUDY DESIGN: Pediatric trauma patients requiring a blood transfusion (red blood cells, fresh frozen plasma, platelets, or cryoprecipitate) within 24 hours of arrival were included. Coagulation values on emergency department arrival were analyzed, as were clinical details and outcome. RESULTS: A total of 102 children (mean age, 6 years; mean injury severity score 22, mean Glascow Coma Scale 7, 80% blunt trauma victims) were studied over a 4 year period. An abnormal prothrombin time was found in 72%, partial thromboplastin time in 38%, fibrinogen in 52%, hemoglobin in 58%, and platelet count in 23%. An abnormal prothrombin time, partial thromboplastin time, and platelet count were strongly associated with mortality (P=.005, .001, and <.0001, respectively) and remained significantly associated in multivariate analysis after adjusting for injury severity score. CONCLUSIONS: Coagulopathy is prevalent in pediatric trauma patients ill enough to require a transfusion and is strongly associated with mortality. Studies are needed to determine whether early coagulation factor replacement and the institution of massive transfusion protocols may improve outcomes in these patients.

Implementation of a pediatric trauma massive transfusion protocol: one institution's experience.

BACKGROUND: Massive transfusion protocols (MTPs) with fixed ratios of blood products may improve outcomes in coagulopathic adult trauma patients. However, there is a paucity of data on transfusion support protocols for pediatric trauma patients, whose mechanisms of injury may differ from those seen in adults. We hypothesized that an MTP would improve outcomes in children, through a balanced blood product resuscitation. STUDY DESIGN AND METHODS: A pediatric trauma MTP, with a fixed ratio of red blood cells (RBCs):fresh-frozen plasma (FFP):platelets:cryoprecipitate in quantities based on the patient's weight, was initiated at a pediatric hospital. Data on clinical status, resuscitation volumes, and hospital course were collected and compared to data from pre-MTP trauma patients requiring transfusion. RESULTS: Fifty-three patients were enrolled over a 15-month period and compared to 49 pre-MTP patients. Seventy-two percent of MTP patients had at least one coagulation value outside of the normal range upon emergency department (ED) arrival, and the median time to FFP transfusion decreased fourfold after MTP implementation (p<0.0001). A total of 49% of MTP patients received greater than 70 mL/kg blood products, and the 24-hour median FFP:RBC transfusion ratio was twofold higher in these patients than the pre-MTP cohort (median, 1:1.8 vs. 1:3.6; p=0.002). No improvement in mortality was observed after MTP implementation, taking into consideration injury severity, prothrombin time, and partial thromboplastin time. CONCLUSIONS: A pediatric trauma MTP is feasible and allows for rapid provision of balanced blood products for transfusion to coagulopathic children. Larger studies are warranted to determine whether such protocols will improve outcomes for pediatric trauma patients.

Cross-sectional study of the effects of self-efficacy on fatigue and pain interference in black women with systemic lupus erythematosus: the role of depression, age and education.

OBJECTIVE: While fatigue and pain are pervasive symptoms in SLE, self-efficacy can mitigate their intensity and impact on patients' daily activity. We examined the relationships of these domains and their interactions with demographics and depression in black women with SLE. METHODS: This is a cross-sectional analysis of data collected among 699 black women with SLE. We used validated, self-reported measures of fatigue, pain interference, symptom self-efficacy, treatment self-efficacy and depression. Linear regression analyses were conducted to examine the relationships between each outcome (fatigue and pain interference) and each predictor (symptom self-efficacy and treatment self-efficacy), and the interaction of demographics and depression. RESULTS: We found inverse associations between fatigue and each of symptom self-efficacy (slope -0.556, p<0.001) and treatment self-efficacy (slope -0.282, p<0.001), as well as between pain interference and each of symptom self-efficacy (slope -0.394, p<0.001) and treatment self-efficacy (slope -0.152, p<0.001). After adjusting for confounders, symptom self-efficacy remained significantly associated with each outcome (adjusted slope -0.241 (p<0.001) and -0.103 (p=0.008) for fatigue and pain, respectively). The amount of decrease in fatigue and pain interference differed by depression severity (p<0.05 for the interaction of symptom self-efficacy and depression). The difference in fatigue by depression widened as symptom self-efficacy increased; the adjusted fatigue scores for moderate/severe depression compared with no depression were 6.8 and 8.7 points higher at mean and high symptom self-efficacy, respectively (p<0.001). Age and education significantly changed the relationship between outcomes and self-efficacy. CONCLUSIONS: Symptom self-efficacy and treatment self-efficacy were inversely related to fatigue and pain interference in black women with SLE. Depression disproportionately increased the intensity of these outcomes. While older women with low symptom self-efficacy reported disproportionately higher pain interference, those with higher education and mean or high levels of symptom self-efficacy reported lower pain interference. These findings may help predict who might benefit most from self-efficacy-enhancing interventions.

Depression, stigma and social isolation: the psychosocial trifecta of primary chronic cutaneous lupus erythematosus, a cross-sectional and path analysis.

OBJECTIVE: Depression is common in individuals with chronic cutaneous lupus erythematosus (CCLE). However, how CCLE may impact patients' psychological well-being is poorly understood, particularly among disproportionally affected populations. We examined the relationships between depression and psychosocial factors in a cohort of predominantly Black patients with primary CCLE (CCLE without systemic manifestations). METHODS: Cross-sectional assessment of individuals with dermatologist-validated diagnosis of primary CCLE. NIH-PROMIS short-forms were used to measure depression, disease-related stigma, social isolation and emotional support. Linear regression analyses (ɑ=0.05) were used to test an a priori conceptual model of the relationship between stigma and depression and the effect of social isolation and emotional support on that association. RESULTS: Among 121 participants (87.6% women; 85.1% Black), 37 (30.6%) reported moderate to severe depression. Distributions of examined variables divided equally among those which did (eg, work status, stigma (more), social isolation (more), emotional support (less)) and did not (eg, age, sex, race, marital status) significantly differ by depression. Stigma was significantly associated with depression (b=0.77; 95% CI0.65 to 0.90), whereas social isolation was associated with both stigma (b=0.85; 95% CI 0.72 to 0.97) and depression (b=0.70; 95% CI0.58 to 0.92). After controlling for confounders, stigma remained associated with depression (b=0.44; 95% CI0.23 to 0.66) but lost significance (b=0.12; 95% CI -0.14 to 0.39) when social isolation (b=0.40; 95% CI 0.19 to 0.62) was added to the model. Social isolation explained 72% of the total effect of stigma on depression. Emotional support was inversely associated with depression in the univariate analysis; however, no buffer effect was found when it was added to the multivariate model. CONCLUSION: Our findings emphasise the psychosocial challenges faced by individuals living with primary CCLE. The path analysis suggests that stigmatisation and social isolation might lead to depressive symptoms. Early clinical identification of social isolation and public education demystifying CCLE could help reduce depression in patients with CCLE.

The Problem of Pain in Systemic Lupus Erythematosus: An Explication of the Role of Biopsychosocial Mechanisms.

OBJECTIVE: To define biopsychosocial mechanisms of pain that go above and beyond disease activity and organ damage in systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional analysis of patient-reported data in a population-based registry of 766 people with SLE. Predictors of pain intensity and interference were examined using hierarchical linear regression. We built 2 main hierarchical regression models with pain intensity and interference as outcomes, both regressed on disease activity and organ damage. For each model, we sought to establish the relationship between pain outcomes and the primary exposures using sequential steps comprising the inclusion of each construct in 6 stages: demographic, socioeconomic, physical, psychological, behavioral, and social factors. We also conducted sensitivity analyses eliminating all overt aspects of pain in the disease activity measure and reestimated the models. RESULTS: Disease activity and organ damage explained 32-33% of the variance in pain intensity and interference. Sociodemographic factors accounted for an additional 4-9% of variance in pain outcomes, whereas psychosocial/behavioral factors accounted for the final 4% of variance. In the sensitivity analyses, we found that disease activity and organ damage explained 25% of the variance in pain outcomes. CONCLUSION: Disease activity only explained 33% of the variance in pain outcomes. However, there was an attenuation in these associations after accounting for psychosocial/behavioral factors, highlighting their roles in modifying the relationship between disease activity and pain. These findings suggest that multilevel interventions may be needed to tackle the negative effect of pain in SLE.

Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants?

OBJECTIVE: To test the hypothesis that red blood cell (RBC) transfusions increase the risk of necrotizing enterocolitis (NEC) in premature infants, we investigated whether the risk of "transfusion-associated" NEC is higher in infants with lower hematocrits and advanced postnatal age. STUDY DESIGN: Retrospective comparison of NEC patients and control patients born at < 34 weeks gestation. RESULTS: The frequency of RBC transfusions was similar in NEC patients (47/93, 51%) and control patients (52/91, 58%). Late-onset NEC (> 4 weeks of age) was more frequently associated with a history of transfusion(s) than early-onset NEC (adjusted OR, 6.7; 95% CI, 1.5 to 31.2; P = .02). Compared with nontransfused patients, RBC-transfused patients were born at earlier gestational ages, had greater intensive care needs (including at the time of onset of NEC), and longer hospital stay. A history of RBC transfusions within 48-hours before NEC onset was noted in 38% of patients, most of whom were extremely low birth weight infants. CONCLUSIONS: In most patients, RBC transfusions were temporally unrelated to NEC and may be merely a marker of overall severity of illness. However, the relationship between RBC transfusions and NEC requires further evaluation in extremely low birth weight infants using a prospective cohort design.

Overcoming barriers to recruitment and retention of African-American women with SLE in behavioural interventions: lessons learnt from the WELL study.

BACKGROUND: African-Americans are historically under-represented in SLE studies and engaging them in behavioural interventions is challenging. The Women Empowered to Live with Lupus (WELL) study is a trial conducted to examine the effectiveness of the Chronic Disease Self-Management Program (CDSMP) among African-American women with SLE. We describe enrolment and retention challenges and successful strategies of the WELL study. METHODS: The Georgians Organized Against Lupus (GOAL) cohort, a population-based cohort established in Atlanta, Georgia, was used to enrol a sample of 168 African-American women with SLE into the CDSMP. The CDSMP is a 6-week, group-based programme led by peers to enhance self-management skills in people with chronic conditions. Study performance standards were predefined and close monitoring of recruitment and retention progress was conducted by culturally competent staff members. Continuous contact with participants, research coordinators' notes and regular research team meetings served to assess barriers and define strategies needed to meet the desired recruitment and retention outcomes. RESULTS: While no substantial barriers were identified to enrol GOAL participants into the WELL study, WELL participants faced difficulties registering for and/or completing (attending ≥4 sessions) a CDSMP workshop. Major barriers were unpredicted personal and health-related issues, misunderstanding of the scope and benefits of the intervention, and transportation problems. Early implementation of tailored strategies (eg, CDSMP scheduled on Saturdays, CDSMP delivered at convenient/familiar facilities, transportation services) helped to reduce participant barriers and achieve a CDSMP registration of 168 participants, with 126 (75%) completers. Frequent contact with participants and compensation helped to reach 92.3% retention for the 6-month survey. CONCLUSIONS: Predefined standards and monitoring of participant barriers by a culturally competent research team and proactive solutions were critical to implementing successful strategies and achieving the desired recruitment and retention outcomes of a behavioural trial involving African-American women with SLE. TRIAL REGISTRATION NUMBER: NCT02988661.

Effect of sequence context and direction of replication on AP site bypass in Saccharomyces cerevisiae.

Yeast can be readily transformed by single-stranded oligonucleotides (ssOligos). Previously, we showed that an ssOligo that generates a 1-nt loop containing an AP site corrected the -1 frameshift mutation in the lys2DeltaA746 allele. However, these experiments had to be performed in yeast apn1 mutants lacking the major AP endonuclease. In this study, we show that bypass of an AP site can be studied in repair-proficient yeast by using ssOligos that generates a 7-nt loop containing an AP site. The bypass studies performed using the ssOligos that generate a 7-nt loop was validated by demonstrating that the result obtained is similar to those derived using ssOligos containing a 1-nt loop in an apn1 mutant. By using the 7-nt loop system, we showed that the bypass efficiencies of AP sites are dependent on the sequence context that surrounds the lesion and are apparently not affected by the direction of DNA replication. In contrast, the mutagenic specificity of an AP site is not affected by the sequence context or the direction of replication. In all cases, dC is inserted at twice the frequency of dA opposite an AP site, indicating that REV1 is mainly responsible for bypass of AP sites at all lesion sites studied.

Patient perceptions and preferences of biologic therapies in SLE.

OBJECTIVE: To evaluate patient perceptions of biologic therapies from a large, population-based cohort of patients with SLE with significant numbers of blacks and whites and across the full spectrum of socioeconomic strata and disease severity. METHODS: This was a cross-sectional study of validated patients with SLE enrolled in the Georgians Organized Against Lupus Cohort between September 2014 and August 2015. The survey instrument was developed ad hoc by the authors and contained an introduction on biologics. RESULTS: A total of 676 participants were on average 48.4 years old with 15.9 years of disease; 93.2% were female and 80.6% were black; 34.2% had private health insurance and 9.8% had no insurance; and 26.8% and 27.5% had Medicare or Medicaid, respectively. Of all respondents, 30.8% had heard of biologics, with a significant difference between blacks and whites (25.2% vs 53.4%, respectively). There were no significant differences, however, between blacks and whites with respect to ever having been on biologics (7.6% and 11.5%, respectively) or where they got their information about biologics. Out of 202 individuals who had heard of biologics, 102 (51.3%) were familiar with potential benefits or side effects, and most (n=129, 66.5%) had a neutral perception to risks associated with biologic use. There was no perception of biologics working differently between races/ethnicities. More (n=76, 62.8%) blacks preferred intravenous over subcutaneous modalities compared with whites (n=12, 37.5%) but were not as willing to pay as much out of pocket for it. Individuals with Medicare were significantly more likely to have been on biologics. CONCLUSIONS: There are important similarities and differences between blacks and whites with lupus with respect to their perceptions of biologic therapies and their impact. There are opportunities to increase patient exposure to information about biologics and improve their understanding in order for them to make the best informed decision possible.

Physician-patient interactions in African American patients with systemic lupus erythematosus: Demographic characteristics and relationship with disease activity and depression.

OBJECTIVE: African American patients with systemic lupus erythematosus (SLE) are at high risk for poor outcomes. Both patient characteristics and the severity of the disease may influence physician-patient interactions, which in turn can impact disease outcomes. We aimed to examine whether patient perceptions of interpersonal processes of care (i.e. physician-patient interactions) varied by demographic characteristics, disease activity, and/or depression in African American patients with SLE. METHODS: The Georgians Organized Against Lupus (GOAL) is a cohort drawn from a population-based registry of people with SLE. We conducted a cross-sectional analysis of patient-reported data collected in 2016-17 among 698 African American participants (out of 863 GOAL participants). We assessed physician-patient interactions (communication, patient-centered decision making, and physician interpersonal style) through the Interpersonal Processes of Care survey (IPC-29), disease activity through the Systemic Lupus Activity Questionnaire, and depression through the Patient Health Questionnaire-9. Mean scores of the IPC-29 scales were compared by gender, age and educational attainment with Wilcoxon rank-sum 2-sample test or Kruskal Wallis test. We conducted linear trend test to examine demographic-adjusted scores of IPC across severity of disease activity and depression, and multivariate logistic regression analyses to examine the association of disease activity and depression with suboptimal IPC scores. RESULTS: Overall, the lowest mean scores were observed for the patient-centered decision making domain, and specifically about how often doctors assessed patients' problems to follow recommendations and treatment among females compared with males (mean scores 3.13 ±â€¯1.42 and 3.64 ±â€¯1.38, respectively; p = 0.015). Mean scores for the assumed socioeconomic level subdomain (how often doctors make assumptions about a patient's socioeconomic level) were worse in individuals aged 18-34 (mean score 1.59 ±â€¯0.94), compared to those aged 35-55 (mean score 1.47 ±â€¯0.94; p = 0.033). Patients with some college or higher educational attainment reported poorer mean scores for most communication and interpersonal style scales than those who reported high-school or less. We found significant linear trends of poorer scores for all communication scales across more severe disease activity and depression symptoms, and poorer scores for all interpersonal style scales across more severe disease activity. Multivariate models revealed that while depression was associated with suboptimal quality of both communication (OR 1.20; 95% CI 1.04-1.39) and interpersonal style (OR 1.12; 95% CI 1.01-1.25), disease activity only increased the odds of suboptimal interpersonal style (OR 1.13; 95% CI 1.03-1.25). CONCLUSION: In the African American population with SLE, suboptimal interactions with providers may be explained in part by the mental and physical symptoms of the patient, regardless of age, gender and education. In addition to standard of care treatment, SLE patients with more severe disease activity and depression might need provider-based interventions focused on communication and interpersonal style.

Chronic Cutaneous Lupus Erythematosus: Depression Burden and Associated Factors.

OBJECTIVES: Depression may occur in up to 30% of individuals with cutaneous lupus erythematosus (CLE), many of whom may also have systemic manifestations. Chronic cutaneous lupus erythematosus (CCLE) conditions are less likely to present systemic involvement than acute and subacute conditions but more often cause permanent scarring and dyspigmentation. However, little is known about depression in those who have CCLE confined to the skin (primary CCLE). As African Americans are at high risk for primary CCLE and depression, we aimed to investigate the prevalence of and explore the risk factors for depression in a population-based cohort of predominantly Black patients with primary CCLE. METHODS: This was a cross-sectional analysis of a cohort of individuals with a documented diagnosis of primary CCLE, established in metropolitan Atlanta, GA, USA. Participants were recruited from the Centers for Disease Control and Prevention (CDC) population-based Georgia Lupus Registry, multicenter dermatology clinics, community practices, and self-referrals. The Patient-Reported Outcomes Measurement Information System (PROMIS) was used to measure the primary outcome: depressive symptoms. Stand-alone questions were used to assess sociodemographics and healthcare utilization. Emotional, informational, and instrumental support were measured with PROMIS short forms, interpersonal processes of care with the IPC-29 survey, and skin-related quality of life with the Skindex-29+ tool. RESULTS: Of 106 patients, 92 (86.8%) were female, 91 (85.8%) were Black, 45 (42.9%) were unemployed or disabled, and 28 (26.4%) reported moderate to severe depressive symptoms. Depression severity was lower in patients who were aged ≥ 60 years, were married, or had graduated from college. Univariate analysis showed that being employed (odds ratio [OR] 0.24; 95% confidence interval [CI] 0.10-0.61), insured (OR 0.23; 95% CI 0.09-0.60), reporting higher instrumental, informational, and emotional support (OR 0.75; 95% CI 0.60-0.94; OR 0.62; 95% CI 0.49-0.78; and OR 0.48; 95% CI 0.35-0.65, respectively), visiting a primary care physician in the last year (OR 0.16; 95% CI 0.04-0.61) and reporting better physician-patient interactions (OR 0.56; 95% CI 0.37-0.87) were negatively associated with depression. Patient's perception of staff disrespect (OR 2.30; 95% CI 1.19-4.47) and worse skin-related quality of life (OR 1.04; 95% CI 1.02-1.06) rendered higher risk. In multivariate analysis, only perception of staff disrespect (OR 2.35; 95% CI 1.06-5.17) and lower emotional support (OR 0.48; 95% CI 0.35-0.66) remained associated with depression. CONCLUSION: Over one-quarter of a predominantly Black population-based cohort of individuals with primary CCLE reported moderate to severe depression, a rate three to five times higher than described previously in the general population from the same metropolitan Atlanta area. Our findings suggest that, while patient's perception of discrimination in the healthcare setting may play a role as a determinant of depression, social support may be protective. In addition to routine mental health screening and depression treatment, interventions directed at providing emotional support and improving office staff interpersonal interactions may contribute to reduce the risk of depression in patients with CCLE.