The impact of social determinants of health on the presentation, management and outcomes of systemic lupus erythematosus.

Disparities in SLE rates and outcomes have been attributed to genetic and hormonal factors, cigarette smoking and environmental pollutants. However, a growing body of research indicates that social determinants of health (SDH) also have substantial impact on the disparities that characterize SLE. According to the World Health Organization, SDH are defined as 'the conditions in which people are born, grow, work, live, and age', account for 30-55% of health outcomes, and adversely impact health outcomes among those of low socioeconomic status and stigmatized racial/ethnic groups. We reviewed the impact of key SDH on SLE presentation, management and outcomes, including income, education, neighbourhood factors, healthcare access, discrimination and social support. We found that adverse SDH conditions may lead to more severe SLE with increased morbidity and mortality, and that SDH affect SLE management by dictating the most feasible monitoring and treatment plan for each individual patient based on his or her specific life circumstances (for example, based on health insurance status, distance to nearest provider and/or drug affordability). SDH also have a significant impact on SLE outcomes, with worse disease and psychosocial outcomes associated with lower income level, lower educational attainment, disadvantaged neighbourhoods, lack of health insurance or public health insurance in the USA, travel burden to nearest provider, anti-Black racism and lower social support. Future efforts to improve the management and outcomes of patients with SLE must combat the societal, economic and political forces that perpetuate these inequities.

Application of the acquired preparedness model for alcohol and cigarette use among reserve-dwelling first nation adolescents.

OBJECTIVE: North American Indigenous youth experience disproportionate harm associated with alcohol and cigarette use compared to other racial/ethnic groups. The Acquired Preparedness Model (APM), developed and tested in primarily White samples, hypothesizes that urgency contributes to risk for substance use by influencing the degree to which adolescents attend to positive aspects of substance use, leading to the development of more positive expectations about the consequences of substance use, and increasing subsequent substance use. The purpose of the present study was to provide an initial test of whether the APM generalizes to understanding alcohol and cigarette use among high-risk First Nation adolescents. METHOD: First Nation adolescents (n = 106, Mage = 14.6, 50.0% female) recruited from reserve communities in Eastern Canada completed self-report measures as part of a larger community-based participatory research project. Procedures were approved by tribal chief, council, and university IRB. RESULTS: The hypothesized model demonstrated excellent fit for alcohol use, χ²(1) = 1.07, p = .30, CFI = 0.99, RMSEA = .03, SRMR = .02, and adequate fit for cigarette use, χ²(1) = 2.58, p = .11, CFI = 0.98, RMSEA = 0.12, SRMR = 0.03. The indirect effects of urgency on alcohol consumption and cigarette smoking through alcohol and cigarette expectancies were each significant. CONCLUSIONS: Findings of the present study provide initial support for the generalizability of the APM in understanding risk for alcohol and cigarette use among reserve-dwelling First Nation youth. The next important step is to replicate this finding in a prospective sample. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Interactions Between Genome-Wide Genetic Factors and Smoking Influencing Risk of Systemic Lupus Erythematosus.

OBJECTIVE: To identify interactions between genetic factors and current or recent smoking in relation to risk of developing systemic lupus erythematosus (SLE). METHODS: For the study, 673 patients with SLE (diagnosed according to the American College of Rheumatology 1997 updated classification criteria) were matched by age, sex, and race (first 3 genetic principal components) to 3,272 control subjects without a history of connective tissue disease. Smoking status was classified as current smoking/having recently quit smoking within 4 years before diagnosis (or matched index date for controls) versus distant past/never smoking. In total, 86 single-nucleotide polymorphisms and 10 classic HLA alleles previously associated with SLE were included in a weighted genetic risk score (wGRS), with scores dichotomized as either low or high based on the median value in control subjects (low wGRS being defined as less than or equal to the control median; high wGRS being defined as greater than the control median). Conditional logistic regression models were used to estimate both the risk of SLE and risk of anti-double-stranded DNA autoantibody-positive (dsDNA+) SLE. Additive interactions were assessed using the attributable proportion (AP) due to interaction, and multiplicative interactions were assessed using a chi-square test (with 1 degree of freedom) for the wGRS and for individual risk alleles. Separate repeated analyses were carried out among subjects of European ancestry only. RESULTS: The mean ± SD age of the SLE patients at the time of diagnosis was 36.4 ± 15.3 years. Among the 673 SLE patients included, 92.3% were female and 59.3% were dsDNA+. Ethnic distributions were as follows: 75.6% of European ancestry, 4.5% of Asian ancestry, 11.7% of African ancestry, and 8.2% classified as other ancestry. A high wGRS (odds ratio [OR] 2.0, P = 1.0 × 10-51 versus low wGRS) and a status of current/recent smoking (OR 1.5, P = 0.0003 versus distant past/never smoking) were strongly associated with SLE risk, with significant additive interaction (AP 0.33, P = 0.0012), and associations with the risk of anti-dsDNA+ SLE were even stronger. No significant multiplicative interactions with the total wGRS (P = 0.58) or with the HLA-only wGRS (P = 0.06) were found. Findings were similar in analyses restricted to only subjects of European ancestry. CONCLUSION: The strong additive interaction between an updated SLE genetic risk score and current/recent smoking suggests that smoking may influence specific genes in the pathogenesis of SLE.

Atlanto-axial Pannus in Patients with and without Rheumatoid Arthritis.

OBJECTIVE: Pannus formation in the atlanto-axial joint is a well-recognized complication of rheumatoid arthritis (RA). Occasionally, atlanto-axial pannus is reported when patients without a history of RA undergo magnetic resonance imaging (MRI) of the cervical spine. We sought to further characterize these patients. METHODS: The Partners HealthCare Research Patient Data Registry was free-text searched for "atlanto-axial" AND "pannus" in cervical spine MRI reports from 2001 to 2015. Cases with MRI reports describing pannus were reviewed. Clinical data were extracted by chart review in cases with confirmed atlanto-axial pannus (n = 105). RESULTS: Twenty-nine patients (27.6%) had RA, all of whom except one carried this diagnosis at the time of the MRI scan. Only 1 of 77 patients without a history of RA was subsequently diagnosed with RA (1.3%, 95% CI 0.1-7.0%, median followup 3.6 yrs). Non-RA patients were significantly older (median age 79 vs 63 yrs, p < 0.0001), less frequently female (55% vs 86%, p = 0.0032), and more likely to have undergone prior cervical spine surgery (18% vs 0%, p = 0.016) compared with RA patients. Thirty-four non-RA patients (44.7%) either had a clinical diagnosis of calcium pyrophosphate dihydrate disease (CPPD) or imaging evidence for tissue calcification. There were no significant differences in age or sex between the CPPD subgroup and other non-RA patients. Twenty-eight patients (26.7%) underwent cervical spine surgery. CONCLUSION: Patients without RA diagnosis and incidental atlanto-axial pannus on cervical spine MRI are unlikely to have previously unrecognized RA. Degenerative disease and tissue calcification may contribute to pannus formation in these patients.

Patterns of use and survival outcomes of positron emission tomography for initial staging in elderly follicular lymphoma patients.

The role of positron emission tomography (PET) in the initial assessment of follicular lymphoma (FL) has been a topic of debate. We examined the patterns of utilization of PET staging in FL and assessed the association of PET with survival. Using the SEER-Medicare database, we identified 5712 patients diagnosed with first primary FL between 2000 and 2009. Older age, African-American race, poor performance status, B-symptoms and history of anemia were negatively associated with PET staging. Receipt of PET staging was positively associated with treatment at institutions affiliated with research networks and with residence in areas with higher concentrations of nuclear medicine specialists. PET was associated with improved lymphoma-related (HR 0.69, 95% CI: 0.58-0.82) and overall (HR 0.75, 95% CI: 0.68-0.83) survival. Our findings substantiate the use of PET as the standard of care for imaging in FL patients. Further investigation is warranted to identify mechanisms underlying the apparent survival advantage associated with PET staging in FL.

Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and Diffuse Large B-Cell Lymphoma Incidence.

OBJECTIVES: Examining the spatial patterns of diffuse large B-cell lymphoma (DLBCL) incidence and residential proximity to toxic release locations may provide insight regarding environmental and sociodemographic risk factors. METHODS: We linked and geocoded cancer incidence data for the period 1999-2008 from the Georgia Comprehensive Cancer Registry with population data from the US Census and the Environmental Protection Agency's Toxics Release Inventory. We conducted cluster analyses and constructed Poisson regression models to assess DLBCL incidence as a function of mean distance to the toxic release sites. RESULTS: In total, 3851 incident DLBCL cases occurred among adults residing in Georgia between 1999 and 2008. Significant focal clustering was observed around 57% of ethylene oxide sites, 5% of benzene sites, 9% of tetrachloroethylene sites, 7% of styrene sites, 10% of formaldehyde sites, 5% of trichloroethylene sites, and 10% of all release sites. Mean distance to sites was significantly associated with DLBCL risk for all chemicals. CONCLUSIONS: Proximity to Toxics Release Inventory sites can be linked to increased DLBCL risk as assessed through focal clustering and Poisson regression, and confirmatory studies using geospatial mapping can aid in further specifying risk factors for DLBCL.

Integrating understanding of epidemiology and genomics in B-cell non-Hodgkin lymphoma as a pathway to novel management strategies.

Non-Hodgkin lymphomas include a biologically and clinically heterogeneous group of cancers distinguished by genetics, histology, and treatment outcomes. New discoveries regarding the genomic alterations and epidemiological exposures associated with these lymphomas have enhanced our understanding of factors that contribute to lymphomagenesis for specific subtypes. We explore the impact of normal B-cell biology engineered for recognizing a wide variety of antigens on the development of specific lymphoma subtypes, review lymphoma genetics, and examine the epidemiology of B-cell NHLs including recent investigations of risk factors for particular lymphoma subtypes based on large pooled analyses. Burkitt lymphoma, an aggressive form of B-cell NHL involving translocation of the MYC gene and an immunoglobulin gene has been associated with a history of eczema, hepatitis C, and occupation as a cleaner. Increased risk of diffuse large B-cell lymphoma has been associated with increased young adult body mass index, history of B-cell-activating autoimmune diseases, hepatitis C, and several single nucleotide variants involving the human leukocyte antigen (HLA) region of chromosome 6 and non-HLA loci near EXOC2, PVT1, MYC, and NCOA1. Tumor sequencing studies suggest that multiple pathways are involved in the development of DLBCL. Additional studies of epidemiological exposures, genome wide associations, and tumor sequencing in follicular, lymphoplasmacytic, marginal zone, and mantle cell lymphoma demonstrate overlapping areas of increased risk factors and unique factors for specific subtypes. Integrating these findings is important for constructing comprehensive models of NHL pathogenesis, which could yield novel targets for therapy and strategies for lymphoma prevention in certain populations.

To Each Its Own: Linking the Biology and Epidemiology of NHL Subtypes.

Non-Hodgkin lymphoma (NHL) constitutes a diverse group of more than 40 subtypes, each characterized by distinct biologic and clinical features. Until recently, pinpointing genetic and epidemiologic risk factors for individual subtypes has been limited by the relative rarity of each. However, several large pooled case-control studies have provided sufficient statistical power for detecting etiologic differences and commonalities between subtypes and thus yield new insight into their unique epidemiologic backgrounds. Here, we review the subtype-specific medical, lifestyle, and biologic components identified in these studies, which suggest that a complex interplay between host genetics, autoimmune disorders, modifiable risk factors, and occupation contributes to lymphomagenesis.

New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy.

Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining the risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology; therefore, until recently, little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining the risk factors for NHL subtypes. We outline the heterogeneity and commonality among the risk factors for NHL subtypes, with proposed subtype-specific as well as shared etiologic mechanisms. In addition, we describe how the study of lymphoma epidemiology may translate into prevention or therapeutic targeting as we continue to explore the complexities of lifestyle and genetic factors that impact lymphomagenesis.

Disease characteristics, patterns of care, and survival in very elderly patients with diffuse large B-cell lymphoma.

BACKGROUND: Although the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients aged >80 years are less clear. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to characterize presentation, treatment, and survival patterns in patients with DLBCL who were diagnosed between 2002 and 2009. Chi-square tests compared characteristics and initial treatments among patients with DLBCL who were aged >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients aged >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. RESULTS: Among 4635 patients with DLBCL, 1156 (25%) were aged >80 years. Patients aged >80 years were less likely to receive R-CHOP and more likely to be observed or receive the combination of rituximab, cyclophosphamide, vincristine, and prednisone (P<.0001 for both). Marital status, stage of disease, disease site, performance status, radiotherapy, and growth factor support were associated with initial R-CHOP in patients aged >80 years. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen found to be associated with improved overall survival (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62) and lymphoma-related survival (hazard ratio, 0.58; 95% confidence interval, 0.38-0.88). CONCLUSIONS: Although patients with DLBCL who were aged >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of treatment of DLBCL on quality of life among patients in this age group.

Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell lymphoma survival: a meta-analysis of gene expression profiling and immunohistochemistry algorithms.

BACKGROUND: Patients with DLBCL exhibit widely divergent outcomes despite harboring histologically identical tumors. Currently, GEP and IHC algorithms assign patients to 1 of 2 main subtypes: germinal center B cell-like (GCB), or activated B cell-like (ABC), the latter of which historically carries a less favorable prognosis. However, it remains controversial as to whether these prognostic groupings remain valid in the era of rituximab therapy. MATERIALS AND METHODS: A systematic literature review identified 24 articles from which meta-analyses were conducted, comparing survival outcomes for patients assigned to either GCB or ABC/non-GCB subtype using GEP and/or Hans, Choi, or Muris IHC algorithms. RESULTS: Patients designated as GCB DLBCL using GEP fared significantly better in terms of overall survival than those with ABC DLBCL (hazard ratio, 1.85; P < .0001). In contrast, the Hans and Choi algorithms failed to identify significant differences in overall survival (P = .07 and P = .76, respectively) between GCB and non-GCB groups. CONCLUSIONS: Our study illustrates a lack of evidence supporting the use of the Hans and Choi algorithms for stratifying patients into distinct prognostic groups. Rather, GEP remains the preferred method for predicting the course of a patient's disease and informing decisions regarding treatment options.

The effect of sunlight on postoperative analgesic medication use: a prospective study of patients undergoing spinal surgery.

OBJECTIVE: Exposure to natural sunlight has been associated with improvement in mood, reduced mortality among patients with cancer, and reduced length of hospitalization for patients who have experienced myocardial infarction. Our aim was to evaluate whether the amount of sunlight in a hospital room modifies a patient's psychosocial health, the quantity of analgesic medication used, and the pain medication cost. METHODS: A prospective study of pain medication use was conducted in 89 patients undergoing elective cervical and lumbar spinal surgery where they were housed on either the "bright" or "dim" side of the same hospital unit. Analgesic medication was converted to standard morphine equivalents for interpatient comparison. The intensity of sunlight in each hospital room was measured daily and psychologic questionnaires were administered on the day after surgery and at discharge. RESULTS: Patients staying on the bright side of the hospital unit were exposed to 46% higher-intensity sunlight on average (p = .005). Patients exposed to an increased intensity of sunlight experienced less perceived stress (p = .035), marginally less pain (p = .058), took 22% less analgesic medication per hour (p = .047), and had 21% less pain medication costs (p = .047). Age quartile was the only other variable found to be a predictor of analgesic use, with a significant negative correlation (p <.001). However, patients housed on the bright side of the hospital consistently used less analgesic medications in all age quartiles. CONCLUSION: The exposure postoperatively of patients who have undergone spinal surgery to increased amounts of natural sunlight during their hospital recovery period may result in decreased stress, pain, analgesic medication use, and pain medication costs.