Association of Systemic Lupus Erythematosus Disease Activity With Choroidal Thickness.

OBJECTIVE: To determine the association between disease activity and choroidal thickness in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a cohort study of 24 SLE patients and 13 healthy controls recruited at Washington University School of Medicine between June 2019 and November 2021. SLE disease activity was assessed using the SLE Disease Activity Index-2000 Responder Index-50 (S2K RI-50). Patients were divided into four groups: high disease activity/no lupus nephritis (HDA/no LN; S2K RI-50 > 4), HDA/active LN (HDA/active LN; S2K RI-50 > 4), low disease activity/inactive LN (LDA/inactive LN; S2K RI-50 ≤ 4), and LDA/no LN (LDA/no LN; S2K RI-50 ≤ 4). LDA/no LN patients were age-, sex-, and race-matched to healthy controls and patients in other SLE groups. Choroidal thickness of the right eye was measured blinded to disease activity on a horizontal section through the fovea on optical coherence tomography images taken within a week of disease assessment. RESULTS: Patients with HDA had choroidal thickening compared with matched patients with LDA. After controlling for multiplicity, choroidal thinning remained statistically significant at 1000 µm nasal to the fovea (308 ± 68 vs 228 ± 64 µm, p = 0.001). Choroidal thickness was not different between LDA/no LN and LDA/inactive LN or healthy controls. CONCLUSION: HDA in patient with SLE is associated with increased choroidal thickness whereas comorbid inactive LN did not affect choroidal thickness. Additional studies in a larger longitudinal cohort are needed to study whether choroidal thickness may be used as a noninvasive, adjunctive measure for disease activity in SLE.

Development of a structured musculoskeletal and rheumatic disease continuing education program for nurse practitioners.

ABSTRACT: The workforce shortage of musculoskeletal and rheumatic disease (MSK-RMD) trained providers has led to the need for additional education for nurse practitioners (NPs) in MSK-RMD. An educational certificate was developed and implemented collaboratively between an academic medical center and a college of nursing. The NP-focused MSK-RMD education program enhanced the assessment and treatment of a variety of common RSK-RMD conditions. Interviews and online surveys were conducted with participants to evaluate the program experience. Participant interviews and survey findings demonstrate overall NP satisfaction with the program. Expanding the program to create an accessible virtual continuing education course may improve accessibility of MSK-RMD education for NPs in primary care and multidisciplinary environments.

Depressed Symptomatology in Systemic Lupus Erythematosus Patients.

OBJECTIVE: Depression is a prevalent (24-30%) and significant comorbidity in patients with systemic lupus erythematosus (SLE). In the present study, we leveraged the longitudinal SLE cohort at the Washington University Lupus Clinic to address 1) what is the longitudinal course of depressed affect among outpatients with SLE and 2) what is the longitudinal relationship between SLE disease activity and depressed affect? METHODS: Longitudinal data from patients with American College of Rheumatology- or Systemic Lupus International Collaborating Clinics-classified SLE were analyzed. Depressed symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression Scale, Revised (CESD-R), and SLE disease activity was measured via the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Group-based trajectory modeling (GBTM) and linear mixed models were used for analysis. RESULTS: The study sample (n = 144) was 56.3% Black and 38.9% White. GBTM revealed 5 distinct groups of patients who demonstrated consistent trends in depression over time. Members of groups 4 (n = 44, 30.6%) and 5 (n = 44, 30.6%) demonstrated CESD-R scores consistent with depression. Of note, Black patients were much more common in group 5 (n = 32, 72.7%, P < 0.02). Analyses identified an association between SLEDAI disease activity and depression scores in multivariate analysis but did not show significance in GBTM and univariate analysis. CONCLUSIONS: The majority (61.2%) of patients had CESD-R scores consistent with persistent depressed affect or major depression over a period of up to 4 years. The lack of a consistent relationship of CESD-R with SLE disease activity highlights the need to regularly monitor, treat, and better understand the causes behind this comorbidity.

Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases.

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p < 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p < 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases.

The Association of Pelvic Bone Mineral Density and With Proximal Femoral and Spine Bone Mineral Density in Post-menopausal Women.

Pelvic fragility fractures result in significant morbidity and their incidence has increased over the past 30 years. One of the main risk factors in skeletal fragility is bone mineral density (BMD). Most of the current literature has focused on understanding spine and hip BMD. We aimed to measure the BMD of pelvis in a cohort of post-menopausal women and compare it to BMD at other skeletal sites. A questionnaire regarding risk factors for osteoporosis was completed by each participant. DXA scan of the pelvis was performed using research software. Three areas of the pelvis corresponding to common fractures were defined on pelvic DXA: R1 = symphysis public, R2 = inferior public rami, R3 = superior public rami. Pelvic BMD was calculated as the average BMD of R1-3. BMD at each location was reported as mean and standard deviation (SD). ANOVA was used to compare BMD between R1-R3 and pelvis, femoral neck, total hip, and spine. Pearson correlation was used to correlate pelvic BMD to BMD of proximal femur and spine. BMD was compared in four participant groups: 1- osteoporosis in spine and hip, 2- osteoporosis in spine only, 3-osteoporosis in hip only, and 4- no osteoporosis in spine and hip. The effect of diabetes and obesity on BMD at various skeletal sites was analyzed. Among the one hundred postmenopausal women enrolled in the study, age was: 64 ± 8, 31% were obese (BMI ≥ 30), and 8% had a diagnosis of type 2 diabetes. Pelvic area R3 had significantly higher BMD than R1 or R2 (p < 0.001). Pelvic BMD (0.50 ± 0.16) was significantly lower than total hip (0.70 ± 0.20) and spine BMD (0.97 ± 0.19) (p < 0.001). Pelvic BMD correlated with BMD at other skeletal locations, with the highest correlation with total hip (total hip: R2: 0.70, femoral neck R2: 0.50, spine R2: 0.65). Pelvic BMD was significantly lower in patients with osteoporosis of both hip and spine compared to the group without osteoporosis at both locations (p = 0.02). Obesity and type 2 diabetes were both associated with significantly higher BMD at pelvis, spine, and total hip. Pelvic BMD is lower than at other skeletal sites and is highly correlated with total hip area bone density. Obesity and type 2 diabetes are associated with higher pelvic BMD. To establish guidelines for the treatment pelvic BMD, studies defining the association of pelvic BMD with pelvic fracture risk are needed.

Anxiety Symptoms Among Patients With Systemic Lupus Erythematosus Persist Over Time and Are Independent of SLE Disease Activity.

OBJECTIVE: The objectives of this study are to identify patterns of anxiety symptomology over time among patients with systemic lupus erythematosus (SLE) and to assess the longitudinal relationship between SLE disease activity and anxiety symptomology. METHODS: Longitudinal data from 139 patients with American College of Rheumatology or Systemic Lupus International Collborating Clinic (SLICC)-classified SLE were analyzed. Anxiety symptomology was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress: Anxiety Short Form 8a. SLE disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 (S2K) and S2K Responder Index 50 (S2K RI-50). Group-based trajectory modeling (GBTM) identified longitudinal trajectories of anxiety symptomology. The relationship between disease activity and anxiety over time was assessed using multilevel linear regressions. RESULTS: The mean patient age was 40.2 years (standard deviation [SD], 12.7); 90.6% were female, and 56.1% were of Black race. All patients had at least three PROMIS anxiety scores over an average of 30.9 months (SD, 13.0). GBTM identified four trajectories of anxiety symptomology, labeled as the following: low (LA), average (AA), moderate (MA), and high anxiety (HA). Black patients were 2.47 (95% confidence interval: 1.19-5.12) times as likely as White patients to be classified into the MA or HA groups compared with the LA or AA groups. On multivariable analysis, active SLE disease was not significantly associated with anxiety over time (P = 0.19). CONCLUSION: Anxiety trajectories remained stable over time, and racial differences in anxiety severity were observed. SLE disease activity was not longitudinally associated with anxiety after controlling for depression and other factors. Further understanding of the factors that contribute to the persistence of anxiety among individuals with SLE is necessary.

SToRytelling to Improve Disease outcomes in Gout (STRIDE-GO): a multicenter, randomized controlled trial in African American veterans with gout.

BACKGROUND: Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs). METHODS: In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence. RESULTS: The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n = 152) or stress reduction video (n = 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p > 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p = 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p = 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p = 0.003), and 6 months, 29.5 vs. 34.5 (p = 0.03), respectively. CONCLUSIONS: A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout. TRIAL REGISTRATION: Registered at ClinicalTrials.gov NCT02741700.

A cohort study of neuropsychological functioning in spouses of U.S. Gulf War veterans.

AIMS: Veterans of the 1991 Gulf War reported symptoms in their spouses that mirrored veterans' symptoms following their return from the war, including problems with attention and memory. Neuropsychological functioning in these spouses has not been examined with objective tests. This study sought to determine if these spouses exhibited deficits in neuropsychological functioning. MAIN METHODS: Spouses of a national cohort of 1991 Gulf War deployed (n = 470) and non-deployed veterans (n = 524) were examined with neuropsychological tests in 1999-2001. KEY FINDINGS: Neuropsychological tests were factor analyzed yielding five factors: verbal memory, visual memory, attention/working memory, visual organization, and motor speed. Spouses of deployed and nondeployed veterans did not differ on mean factor scores, percentage of impaired factors, or individual test scores. Spouse attention/working memory was related to their having diagnoses of PTSD or anxiety disorders, or self-reported symptoms of current anxiety. Spouse visual memory was related to a diagnosis of current depression. Spouse motor speed was related to their own status of having chronic multisymptom illness (CMI). SIGNIFICANCE: Spouses of Gulf War deployed and nondeployed veterans demonstrated similar neuropsychological functioning, although spouses with psychiatric diagnoses and symptoms, or CMI demonstrated neuropsychological impairments characteristic of those conditions, suggesting that monitoring spouses for these conditions and impairments may be warranted. This pattern of relative weaknesses mirrors some of the previously reported findings for Gulf War veterans, although the veterans displayed neuropsychological impairments beyond what was accounted for by these conditions.

Cognitive dysfunction among people with systemic lupus erythematosus is associated with reduced participation in daily life.

OBJECTIVES: This study aimed to investigate the distribution of cognitive function in people with systemic lupus erythematosus (SLE) by objective and self-report measures and associations between cognition and participation among people with SLE. METHODS: Fifty-five volunteers with SLE (age: 39.7 ± 12.7yrs, female: 92.7%) completed the Montreal Cognitive Assessment (MoCA) to measure cognitive ability objectively, the Cognitive Symptom Inventory (CSI) and PROMIS Cognitive Function 8a (CF) to assess self-reported everyday cognition, and PROMIS-43 Profile to assess self-reported ability to participate in social roles and activities (participation) and other disease-associated symptoms (e.g., depression, pain, fatigue). RESULTS: The average MoCA score was 25.3 ± 3.1, with 47.3% of participants scoring <26, which is indicative of cognitive impairment. Group average CSI (35.8 ± 7.9), CF (T-score = 45.0 ± 8.5), and participation (T-score = 46.9 ± 11.2) scores suggest mildly impaired functional cognition and participation compared to normative data. Participation correlated with self-reported everyday cognition measures (r ≥ 0.56, p < 0.01) but not with MoCA (r = 0.25, p = 0.06). In hierarchical linear regression analysis, CSI, fatigue, and pain were each significant independent predictors of participation (R2 = 0.78, p < 0.01). CONCLUSIONS: We found that cognitive dysfunction is common among people with SLE. Along with pain and fatigue, reduced everyday cognitive function contributes to reduced participation in social, leisure, work, and family-related activities.

Effect of peripheral neuropathy on bone mineral density in adults with diabetes: A systematic review of the literature and meta-analysis.

INTRODUCTION: Peripheral neuropathy occurs in two thirds of patients with diabetes mellitus (DM). It can lead to severe pathological changes in the feet, and it increases the risk of fracture more than any other diabetic complication. The objective of this review is to analyze available literature on the effect of peripheral neuropathy on BMD of the foot, spine, or hip. We hypothesize that the presence of diabetic neuropathy leads to lower BMD in adults with diabetes. METHODS: Original studies investigating the effects of diabetic neuropathy on bone density were searched for inclusion in this systematic review. Studies were eligible if they met the following criteria: 1) participants included adults with either Type 1 DM or Type 2 DM; 2) Method used for the diagnosis of neuropathy described in the manuscript 3) DXA scan, ultrasound, or CT scan was used to measure proximal femur, spine, or foot bone mineral density were reported, and 4) bone parameters were analyzed based on the presence and absence of neuropathy. RESULTS: Among the 5 studies that met eligibility criteria, 4 did not find a significant effect of neuropathy on BMD. One study showed a significant negative impact of neuropathy on calcaneal BMD in patients with type 1 diabetes. The meta-analysis did not show a significant effect of peripheral neuropathy on BMDs of proximal femur, spine, and calcaneus in diabetic adults. CONCLUSION: Our study shows no evidence that peripheral neuropathy affects bone density or bone turnover in DM. However, this conclusion should be taken with caution since only a very limited number of studies were available for inclusion in the analysis and included both type 1 and type 2 DM patients. Improved measures of peripheral neuropathy and more advanced imaging technologies are needed to better assess the effect of diabetes on bone health.

Development and validation of lupus nephritis case definitions using United States veterans affairs electronic health records.

OBJECTIVE: International Classification of Diseases (ICD) codes are commonly used to identify patients with rare diseases in electronic health records (EHRs). However, misclassification is common, impacting the validity of study results. In this study, we compared the accuracies of several ICD-based case definitions of lupus nephritis (LN) in identifying United States veterans with LN. METHODS: Using the Department of Veterans Affairs (VA) EHR, we identified all veterans with ≥1 ICD-9 or 10 diagnostic codes for systemic lupus erythematosus (SLE) between October 1, 1999 and September 30, 2017. A cohort was randomly selected for diagnostic validation and 9 ICD-based LN case definitions were applied to this cohort. The diagnostic accuracy of each definition was assessed against gold standard criterion of biopsy-proven LN. RESULTS: 18,420 veterans had ≥1 ICD-9 or 10 diagnostic codes for SLE; 981 were randomly selected for diagnostic validation. 95 veterans (9.7%) had biopsy-proven LN. The case definitions had high specificity and NPV but variable sensitivity and PPV. The definition containing ≥2 ICD -9 codes for SLE and ≥2 nephritis indicators had the highest combination of sensitivity and specificity (87.4% and 94.6% respectively). ICD-10 code for LN had high specificity (99.8%) and PPV (93.9%). CONCLUSION: ICD-based case definitions of LN in the VA population have high specificity and NPV but variable sensitivity and PPV. Our results may help guide the design of future LN studies in VA cohorts. The choice of specific case definitions depends on the relative importance of different accuracy measures to individual studies.

Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort.

OBJECTIVES: Although cross-sectional studies have shown that ankylosing spondylitis-specific factors correlate with depressive symptom severity, the association of these factors over time is unresolved. We examined the demographic and clinical factors associated with longitudinal depressive symptom severity in AS patients. METHODS: We analyzed sociodemographic, clinical, behavioral and medication data from 991 patients from the Prospective Study of Outcomes in Ankylosing spondylitis cohort, and measured depression severity with the Center for Epidemiological Studies Depression (CES-D) Scale administered at approximately 6-month visit intervals. Multivariable longitudinal negative binomial regression models were conducted using generalized estimating equation modeling to assess the demographic, clinical, and medication-related factors associated with depression severity by CES-D scores over time. RESULTS: The median baseline CES-D score (possible range 0-60) was 10.0 (interquartile range = 5, 17). In longitudinal multivariable analyses, higher CES-D scores were associated with longitudinal smoking, greater functional impairment, greater disease activity, self-reported depression, and poor global health scores. Marital status (e.g., being married) was associated with lower CES-D. Adjusted mean CES-D scores in our model decreased over time, with a significant interaction between time and gender observed. CONCLUSION: This study identified longitudinal clinical factors such as greater disease activity, greater functional impairment, and poor global health to be associated with longitudinal depression severity. These factors are potentially modifiable and may help manage depressive symptoms in AS.

Mental health in spouses of U.S. Gulf War veterans.

Veterans' spouses are at risk for mental distress and substance use. We examined long term psychological functioning in spouses from a national cohort of 1991 Gulf War era veterans. From clinical interviews, spouses of deployed veterans (n = 488) did not have a greater prevalence of post-war mental disorders compared to spouses of non-deployed veterans (n = 536); however, in couples that were living together since the war, there was an increased risk of anxiety disorders or any one disorder. On questionnaires, the impact varied but was most consistently observed in more severe depression and greater functional impairment in spouses of deployed compared to non-deployed veterans. If a veteran developed post-war anxious/depressive disorders or any one mental disorder, the matched spouse was more likely to develop post-war anxious/depressive disorders or any one mental disorder, respectively. Veteran combat exposure did not similarly increase the risk of spouse post-war mental disorders. Greater spouse self-reported symptomatology was observed in spouses of veterans with anxious/depressive disorders even when controlling for deployment. In summary, the war conferred greater risk for spouse mental disorders and distress for spouses of veterans with mental health disorders, with some increased risk for spouses of deployed veterans, especially in couples together since the war.

Gout Self-Management in African American Veterans: A Qualitative Exploration of Challenges and Solutions From Patients' Perspectives.

OBJECTIVE: To explore gout self-management and associated challenges and solutions in African Americans. METHODS: We conducted semistructured interviews with 35 African American veterans with gout, who received health care at Birmingham or Philadelphia Veterans Affairs (VA) medical centers, had filled urate-lowering therapy (ULT; most commonly allopurinol) for at least 6 months, and had a ULT medication possession ratio ≥80%. The interview protocol was constructed to explore key concepts related to gout self-management, including initial diagnosis of gout, beginning medical care for gout, the course of the gout, ULT medication adherence, dietary strategies, comorbidity and side effects, and social support. RESULTS: Thirty-five African American male veterans with gout who had ≥80% ULT adherence (most commonly, allopurinol) were interviewed at Birmingham (n = 18) or Philadelphia (n = 17) VA medical centers. Mean age was 65 years, mean body mass index was 31.9 kg/m2 , 97% had hypertension, 23% had coronary artery disease, and 31% had renal failure. The main themes motivating African American veterans to better gout self-management were fear of pain, adherence to medications, self-discipline, lifestyle changes, information gathering, and developing a positive outlook. Birmingham participants more frequently revealed skipping gout medications. More Philadelphia participants discussed lifestyle/diet changes to prevent gout flares, indicated limiting social activities that involved drinking, and sought more information about gout self-management from health care providers and internet sources. CONCLUSION: Identified themes, including cultural differences by site, led to the development of a patient-centered intervention to improve gout self-management in African American men with gout.

Evaluating the Productivity of VA, NIH, and AHRQ Health Services Research Career Development Awardees.

PURPOSE: To evaluate the academic advancement and productivity of Department of Veterans Affairs Health Services Research and Development (HSR&D) Career Development Award (CDA) program recipients, National Institutes of Health (NIH) K awardees in health services research (HSR), and Agency for Healthcare Research and Quality (AHRQ) K awardees. METHOD: In all, 219 HSR&D CDA recipients from fiscal year (FY) 1991 through FY2010; 154 NIH K01, K08, and K23 awardees FY1991-FY2010; and 69 AHRQ K01 and K08 awardees FY2000-FY2010 were included. Most data were obtained from curricula vitae. Academic advancement, publications, grants, recognition, and mentoring were compared after adjusting for years since award, and personal characteristics, training, and productivity prior to the award. RESULTS: No significant differences emerged in covariate-adjusted tenure-track academic rank, number of grants as primary investigator (PI), major journal articles as first/sole author, Hirsch h-index scores, likelihood of a journal editorship position or membership in a major granting review panel, or mentoring postgraduate researchers between the HSR&D CDA and NIH K awardees from FY1991-FY2010, or among the three groups of awardees from FY2000 or later. Among those who reported grant funding levels, HSR&D CDAs from FY1991-2010 had been PI on more grants of $100,000 than NIH K awardees. HSR&D CDAs had a higher mean number of major journal articles than NIH K awardees from FY1991-2010. CONCLUSIONS: Findings show that all three HSR career development programs are successfully selecting and mentoring awardees, ensuring additional HSR capacity to improve the quality and delivery of high-value care.

Tumor Necrosis Factor Inhibition and Head and Neck Cancer Recurrence and Death in Rheumatoid Arthritis.

The objective of this retrospective cohort study was to determine the effect of tumor necrosis factor inhibitor (TNFi) therapy on the risk of head and neck cancer (HNC) recurrence or HNC-attributable death in patients with rheumatoid arthritis (RA). RA patients with HNC were assembled from the US national Veterans' Affairs (VA) administrative databases, and diagnoses confirmed and data collected by electronic medical record review. The cohort was divided into those treated with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) versus TNF inhibitors (TNFi) after a diagnosis of HNC. Likelihood of a composite endpoint of recurrence or HNC-attributable death was determined by Cox proportional hazards regression. Of 180 patients with RA and HNC, 31 were treated with TNFi and 149 with nbDMARDs after the diagnosis of HNC. Recurrence or HNC-attributable death occurred in 5/31 (16.1%) patients in the TNFi group and 44/149 (29.5%) patients in the nbDMARD group (p = 0.17); it occurred in 2/16 (13%) patients who received TNFi in the year prior to HNC diagnosis but not after. Overall stage at diagnosis (p = 0.03) and stage 4 HNC (HR 2.49 [CI 1.06-5.89]; p = 0.04) were risk factors for recurrence or HNC-attributable death; treatment with radiation or surgery was associated with a lower risk (HR 0.35 [CI 0.17-0.74]; p = 0.01 and HR 0.39 [CI 0.20-0.76]; p = 0.01 respectively). Treatment with TNFi was not a risk factor for recurrence or HNC-attributable death (HR 0.75; CI 0.31-1.85; p = 0.54). We conclude that treatment with TNFi may be safe in patients with RA and HNC, especially as the time interval between HNC treatment and non-recurrence increases. In this study, TNF inhibition was not associated with an increase in recurrence or HNC-attributable death.

Associations between obsessive-compulsive classes and pathological gambling in a national cohort of male twins.

IMPORTANCE: Because of shared characteristics, pathological gambling (PG) has been variously conceptualized as an obsessive-compulsive (OC) spectrum disorder or as an addictive disorder. Prior community-based studies have not systematically determined the association between PG and OC features and whether common genetic factors contribute to both conditions. OBJECTIVE: To examine the association and genetic correlation between PG and OC features. DESIGN, SETTING, AND PARTICIPANTS: We performed a latent class analysis (LCA) of OC features, cross-sectional tests of association, and classic twin genetic analysis using results of telephone interviews conducted from March 2002 through November 2003. Participants included 1675 male twin pairs from the Vietnam Era Twin Registry, aged 45 to 60 years. MAIN OUTCOMES AND MEASURES: Ten OC features were queried and used to derive OC classes identified via LCA. RESULTS: The best-fitting LCA model identified the following 4 OC classes: unaffected (class 1), ritual/symmetry compulsions (class 2), germ/contamination obsessions (class 3), and severe OC (class 4). All PG symptoms were more common in class 4 OC and 6 of 10 PG symptoms were significantly more common in class 4 OC (P < .01). Participants in the severe class were most likely to have 4 or more DSM-IV or DSM-5 PG diagnostic criteria (odds ratio, 3.8 [95% CI, 1.8-8.2]). The genetic correlation between phenotypes was 0.44 (95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE: The association between OC features and diagnostic criteria for PG highlights a role of obsessions and compulsivity in PG, and the lifetime co-occurrence of these disorders results in part from common genetic variance. Phenotypic and genetic overlap between OC features and PG add to our understanding of the most appropriate classification of PG and offers insights for treatment development.

Myocardial infarction risk among patients with fractures receiving bisphosphonates.

OBJECTIVE: To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. RESULTS: After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. CONCLUSION: Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.