The Natural History of Knee Osteoarthritis Pain Experience and Risk Profiles.

The study aimed to characterize the natural history of the pain experience, concurrently considering intermittent and constant pain over 4 years, and determine baseline factors associated with unfavorable trajectories in individuals with chronic knee pain. The Osteoarthritis Initiative (OAI) is a prospective, observational study of people with or at higher risk for knee osteoarthritis. The Intermittent and Constant Osteoarthritis Pain (ICOAP) was assessed annually at 48-to-96-month OAI visits. Twenty-eight baseline sociodemographic, knee-specific, and health-related characteristics were assessed. Group-based dual-trajectory modeling identified pain experience patterns indicated by ICOAP intermittent and constant pain scores over 4 years. Multivariable multinomial logistic regression models determined baseline factors associated with membership in each dual-trajectory group. Four longitudinal pain experience patterns were identified (n = 3,584, mean age = 64.8 [standard deviation 9.0] years, BMI = 28.6 [5.0] kg/m2; 57.9% women). Group 1 (37.7%) had minimal intermittent and no constant pain; Group 2 (35.1%) had mild intermittent and no constant pain; Group 3 (18.5%) had mild intermittent and low-grade constant pain; and Group 4 (8.7%) had moderate intermittent and constant pain. Baseline widespread pain, knee stiffness, back pain, hip pain, ankle pain, obesity, depressive symptoms, more advanced radiographic disease, and analgesic use were each associated with an increased risk of membership in less favorable Groups 2, 3, and 4. These distinct courses of pain experience may be driven by different underlying pain mechanisms. The benchmarked ICOAP scores could be used to stratify patients and tailor management. Addressing and preventing the development of modifiable risks (eg, widespread pain and knee joint stiffness) may reduce the chance of belonging to unfavorable dual-trajectory groups. PERSPECTIVE: Concurrently tracking intermittent versus constant pain experience, group-based dual-trajectory modeling identified 4 distinct pain experience patterns over 4 years. The benchmarked ICOAP scores in these dual trajectories could aid in stratifying patients for tailored management strategies and intensity of care.

Pembrolizumab Added to Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Relapsed or Refractory Classic Hodgkin Lymphoma: A Multi-institutional Phase 2 Investigator-Initiated Nonrandomized Clinical Trial.

Importance: To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant. Objective: To evaluate the complete response rate as assessed by 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma. Design, Setting, and Participants: A single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT. Interventions: Two cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment. Main Outcomes and Measures: The primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety. Results: Forty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting. Conclusions and Relevance: Results suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant. Trial Registration: ClinicalTrials.gov Identifier: NCT03077828.

Use of Popular Opinion Leader Models to Disseminate Information About Clinical Trials to Black Individuals With Lupus in Two US Cities.

OBJECTIVE: Clinical trials for systemic lupus erythematosus ("lupus") under enroll Black individuals despite higher disease prevalence, morbidity, and mortality among Black compared to White individuals. To begin to address this disparity, we leveraged community-academic partnerships in 2 US cities (Boston and Chicago) to train popular opinion leaders (POLs) to disseminate information about clinical trials in predominantly Black communities. METHODS: The team of community and academic partners collaboratively developed a 5-module curriculum about clinical trials, barriers, facilitators, and structural racism in research. We enrolled POLs in Boston and Chicago to participate virtually in the curriculum and assessed knowledge gained by comparing pre- and post-test scores. We described the POLs' ability to disseminate information about clinical trials through their communities. RESULTS: We enrolled 19 POLs in Boston and 16 in Chicago; overall, 71% reported a lupus diagnosis, 94% were female, and 80% self-identified as Black or African American. The program was adapted to virtual formats due to the COVID-19 pandemic. POLs demonstrated significant improvement comparing pre/post scores for the conduct of clinical trials and history of racism in clinical research. Fifteen POLs (43%) reported their dissemination of information about clinical trials. Information reached 425 community members in Boston (90% virtually) and 1,887 in Chicago (95% virtually). CONCLUSION: By leveraging community-academic partnerships, we developed and implemented a curriculum to promote familiarity with clinical trials, leading to information dissemination by POLs in predominantly Black communities that are underrepresented in lupus clinical trials. The program successfully transitioned to a virtual model during the COVID-19 pandemic.

Ambulatory support moment contribution patterns and MRI-detected tibiofemoral and patellofemoral disease worsening in adults with knee osteoarthritis: A preliminary study.

We investigated whether baseline sagittal-plane ankle, knee, and hip contribution to the total support moment (TSM) are each associated with baseline-to-2-year tibiofemoral and patellofemoral tissue damage worsening in adults with knee osteoarthritis. Ambulatory lower-limb kinetics were captured and computed. TSM is the sum of ankle, knee, and hip extensor moments at each instant during gait. Ankle, knee, and hip contributions to TSM were computed as joint moments divided by TSM, expressed as percentages. Participants underwent MRI of both knees at baseline and 2 years later. Logistic regression models assessed associations of baseline ankle contribution to TSM with baseline-to-2-year cartilage damage and bone marrow lesion worsening, adjusted for age, sex, BMI, gait speed, disease severity, and pain. We used similar analytic approaches for knee and hip contributions to TSM. Sample included 391 knees from 204 persons (age[SD]: 64[10] years; 76.5% women). Greater ankle contribution may be associated with increased odds of tibiofemoral cartilage damage worsening (OR = 2.38; 95% CI: 1.02-5.57) and decreased odds of patellofemoral bone marrow lesion worsening (OR = 0.14; 95% CI: 0.03-0.73). The ORs for greater knee contribution were in the protective range for tibiofemoral compartment and in the deleterious range for patellofemoral. Greater hip contribution may be associated with increased odds of tibiofemoral worsening (OR = 2.71; 95% CI: 1.17-6.30). Greater ankle contribution to TSM may be associated with baseline-to-2-year tibiofemoral worsening, but patellofemoral tissue preservation. Conversely, greater knee contribution may be associated with patellofemoral worsening, but tibiofemoral preservation. Preliminary findings illustrate potential challenges in developing biomechanical interventions beneficial to both tibiofemoral and patellofemoral compartments.

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma.

In a multicenter, phase 2, investigator-initiated trial of sequential pembrolizumab and AVD (doxorubicin, vinblastine, and dacarbazine), nearly two-thirds of patients with untreated, unfavorable, or advanced-stage classic Hodgkin lymphoma (cHL) achieved positron emission tomography (PET)-defined, complete or near-complete metabolic responses (CMRs), following pembrolizumab monotherapy. Furthermore, all patients achieved CMR after 2 cycles of AVD, with 100% of patients alive and without relapse at initial publication. We now report long-term follow-up, including the 3-year overall survival (OS) and planned correlative analyses. Thirty patients received 3 cycles of single-agent pembrolizumab, followed by AVD chemotherapy for 4 to 6 cycles depending on the stage and bulk. PET/computed tomography scan was performed after pembrolizumab monotherapy, 2 cycles of AVD, and at the end of therapy. Baseline biopsy samples were analyzed for genomic alterations of chromosome 9p24.1 and programmed cell death protein 1 (PD-1) pathway markers. At a median follow-up of 33.1 months (range, 26.0-43.0), progression-free survival and OS remained 100%. All patients had genomic alterations in 9p24.1 and were positive for programmed death ligand 1 (PD-L1) by immunohistochemistry. There was no relationship between depth of response to single-agent pembrolizumab and 9p24.1 alterations or PD-1 pathway H-scores. After additional follow-up, sequential pembrolizumab and AVD remained highly effective. The high response rates observed at all PD-L1 levels suggest that even low levels of PD-L1 expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase 2 trial (registered at www.clinicaltrials.gov as #NCT03226249) is ongoing to confirm our findings.

Motivational interviewing intervention for increasing physical activity and improving dietary behaviors: The Lupus Intervention Fatigue Trial protocol.

The Lupus Intervention Fatigue Trial (LIFT) is a prospective, randomized controlled trial to assess the effectiveness of a six-month motivational interviewing intervention program versus an educational control to reduce fatigue in persons with systematic lupus erythematosus (SLE). Participants are randomized using a stratified, 1:1 allocation design to the LIFT intervention or control arm. We plan to enroll 236 participants to achieve the target of 200 persons with six-month follow-up for the primary endpoint. Specific aims of this study are to evaluate the impact of the LIFT intervention on 1) self-reported measures of fatigue and 2) impact on accelerometer-measured physical activity. The primary study outcome is six-month change in fatigue from baseline, assessed by the Fatigue Severity Score (FSS). Additional outcomes include objective measures of physical activity, including non-sedentary behavior and moderate-to-vigorous activity (secondary outcome), and adherence to the LIFT dietary intervention, as assessed by nutrient density (diet quality) and recommended food groups/eating patterns (exploratory outcome) in persons with SLE. Intervention effectiveness will be assessed using an intention-to-treat two-arm comparison of six-month change in FSS, with one interim monitoring analysis. A two-sample independent group t-test will compare the six-month changes in FSS between the study arms. Intervention effect durability will be assessed 12-months after baseline (6 months after completion of the intervention). Enrollment began in June 2019 and is expected to end in June 2023. This study will inform future intervention strategies that promote physical activity and improved diet quality to reduce fatigue in persons with SLE.

Knee Confidence Trajectories Over Eight Years and Factors Associated With Poor Trajectories in Individuals With or at Risk for Knee Osteoarthritis.

OBJECTIVE: To identify distinct trajectories of lack of knee confidence over an 8-year follow-up period and to examine baseline factors associated with poor trajectories in individuals with or at risk for knee osteoarthritis (OA). METHODS: The Osteoarthritis Initiative is a prospective cohort study of individuals with or at high risk for knee OA. Confidence in the knees was assessed within the Knee Injury and Osteoarthritis Outcome Score instrument querying how much the individual is troubled by lack of confidence in his/her knee(s), rated as not-at-all (score = 0), mildly (score = 1), moderately (score = 2), severely (score = 3), and extremely (score = 4) troubled, reported annually from baseline to 96 months. Lack of knee confidence was defined as a score of ≥2. We used latent class models to identify subgroups that share similar underlying knee confidence trajectories over an 8-year period and multivariable multinomial logistic regression models to examine baseline factors associated with poor trajectories. RESULTS: Among 4,515 participants (mean ± SD age 61.2 ± 9.2 years, mean ± SD BMI 28.6 ± 4.8 kg/m2 ; 2,640 [58.5%] women), 4 distinct knee confidence trajectories were identified: persistently good (65.6%); declining (9.1%); poor, improving (13.9%); and persistently poor (11.4%). Baseline predictors associated with persistently poor confidence (reference: persistently good) were younger age, male sex, higher body mass index (BMI), depressive symptoms, more advanced radiographic disease, worse knee pain, weaker knee extensors, history of knee injury and surgery, and reported hip and/or ankle pain. CONCLUSION: Findings suggest the dynamic nature of self-reported knee confidence and that addressing modifiable factors (e.g., BMI, knee strength, depressive symptoms, and lower extremity pain) may improve its long-term course.

Comprehensive evaluation of bronchoalveolar lavage from patients with severe COVID-19 and correlation with clinical outcomes.

Information on bronchoalveolar lavage (BAL) in patients with COVID-19 is limited, and clinical correlation has not been reported. This study investigated the key features of BAL fluids from COVID-19 patients and assessed their clinical significance. A total of 320 BAL samples from 83 COVID-19 patients and 70 non-COVID-19 patients (27 patients with other respiratory viral infections) were evaluated, including cell count/differential, morphology, flow cytometric immunophenotyping, and immunohistochemistry. The findings were correlated with clinical outcomes. Compared to non-COVID-19 patients, BAL from COVID-19 patients was characterized by significant lymphocytosis (p < 0.001), in contrast to peripheral blood lymphopenia commonly observed in COVID-19 patients and the presence of atypical lymphocytes with plasmacytoid/plasmablastic features (p < 0.001). Flow cytometry and immunohistochemistry demonstrated that BAL lymphocytes, including plasmacytoid and plasmablastic cells, were composed predominantly of T cells with a mixture of CD4+ and CD8+ cells. Both populations had increased expression of T-cell activation markers, suggesting important roles of helper and cytotoxic T-cells in the immune response to SARS-CoV-2 infection in the lung. More importantly, BAL lymphocytosis was significantly associated with longer hospital stay (p < 0.05) and longer requirement for mechanical ventilation (p < 0.05), whereas the median atypical (activated) lymphocyte count was associated with shorter hospital stay (p < 0.05), shorter time on mechanical ventilation (p < 0.05) and improved survival. Our results indicate that BAL cellular analysis and morphologic findings provide additional important information for diagnostic and prognostic work-up, and potential new therapeutic strategies for patients with severe COVID-19.

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

Association of Long-term Strenuous Physical Activity and Extensive Sitting With Incident Radiographic Knee Osteoarthritis.

Importance: Persons with knee symptoms recognize the health benefits of engaging in physical activity, but uncertainty persists about whether regular strenuous physical activity or exercise can accelerate tissue damage. A sedentary lifestyle of inactivity or underloading may also be associated with deleterious joint health. Objective: To establish whether long-term strenuous physical activity participation and extensive sitting behavior are each associated with increased risk of developing radiographic knee osteoarthritis (KOA) in individuals at high risk for the disease. Design, Setting, and Participants: This cohort study analyzed data from the Osteoarthritis Initiative, a prospective longitudinal cohort study of men and women with or at an increased risk of developing symptomatic, radiographic KOA. Community-dwelling adults were recruited from 4 US sites (Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island) and were followed up for up to 10 years. Individuals were included if they had a baseline Kellgren and Lawrence grade of 0 in both knees and completed a PASE (Physical Activity Scale for the Elderly) questionnaire at baseline and at least 2 follow-up visits over an 8-year interval. Data analyses were conducted from May 2018 to November 2018. Exposures: Baseline to 8-year trajectories of strenuous physical activity participation and extensive sitting behavior were identified using group-based trajectory models. Main Outcomes and Measures: Incident radiographic KOA, defined as Kellgren and Lawrence grade 2 or higher in either knee by the 10-year follow-up visit. Results: A total of 1194 participants were included in the sample (697 women [58.4%]), with a baseline mean (SD) age of 58.4 (8.9) years and mean body mass index (BMI) of 26.8 (4.5). Four distinct trajectories of weekly hours spent in strenuous physical activities and 3 distinct trajectories of extensive sitting were identified. Long-term engagement in low-to-moderate physical activities (adjusted odds ratio [OR], 0.69; 95% CI, 0.48-1.01) or any strenuous physical activities (adjusted OR, 0.75; 95% CI, 0.53-1.07) was not associated with 10-year incident radiographic KOA. Persistent extensive sitting was not associated with incident KOA. Despite relatively mild symptoms and high function in this early-stage sample, 594 participants (49.7%) did not engage in any strenuous physical activities (ie, 0 h/wk) across 8 years, and 507 (42.5%) engaged in persistent moderate-to-high frequency of extensive sitting. Older age, higher BMI, more severe knee pain, non-college graduate educational level, weaker quadriceps, and depression were each associated with a persistent lack of engagement in strenuous physical activities. Conclusions and Relevance: Results from this study appeared to show no association between long-term strenuous physical activity participation and incident radiographic KOA. The findings raise the possibility of a protective association between incident KOA and a low-to-moderate level of strenuous physical activities.

Development and validation of risk stratification trees for incident slow gait speed in persons at high risk for knee osteoarthritis.

OBJECTIVES: Disability prevention strategies are more achievable before osteoarthritis disease drives impairment. It is critical to identify high-risk groups, for strategy implementation and trial eligibility. An established measure, gait speed is associated with disability and mortality. We sought to develop and validate risk stratification trees for incident slow gait in persons at high risk for knee osteoarthritis, feasible in community and clinical settings. METHODS: Osteoarthritis Initiative (derivation cohort) and Multicenter Osteoarthritis Study (validation cohort) participants at high risk for knee osteoarthritis were included. Outcome was incident slow gait over up to 10-year follow-up. Derivation cohort classification and regression tree analysis identified predictors from easily assessed variables and developed risk stratification models, then applied to the validation cohort. Logistic regression compared risk group predictive values; area under the receiver operating characteristic curves (AUCs) summarised discrimination ability. RESULTS: 1870 (derivation) and 1279 (validation) persons were included. The most parsimonious tree identified three risk groups, from stratification based on age and WOMAC Function. A 7-risk-group tree also included education, strenuous sport/recreational activity, obesity and depressive symptoms; outcome occurred in 11%, varying 0%-29 % (derivation) and 2%-23 % (validation) depending on risk group. AUCs were comparable in the two cohorts (7-risk-group tree, 0.75, 95% CI 0.72 to 0.78 (derivation); 0.72, 95% CI 0.68 to 0.76 (validation)). CONCLUSIONS: In persons at high risk for knee osteoarthritis, easily acquired data can be used to identify those at high risk of incident functional impairment. Outcome risk varied greatly depending on tree-based risk group membership. These trees can inform individual awareness of risk for impaired function and define eligibility for prevention trials.

Addressing Lupus Health Disparities: The MONARCAS Community and Academic Collaborative Program.

Purpose: The Centers for Disease Control (CDC) Popular Opinion Leader (POL) model was implemented in a lupus education program (MONARCAS) for the Latino community. The program aim was to increase lupus awareness by training high school students, community health workers, and parents. Methods: A curriculum was developed training POLs to disseminate concepts about lupus signs and symptoms. Pre- and post-program questions assessed lupus knowledge and message dissemination. Results: POL groups represented distinct demographic characteristics with Spanish or English language dominance. POLs reported increased lupus knowledge and program satisfaction. Conclusions: Future program goals should aim to increase understanding and improving access to care for Latino communities affected by lupus.

Parenting Desires Among Individuals Living With Human Immunodeficiency Virus in the United States.

BACKGROUND: In 1988, 1 of 3 women (W) and heterosexual men living with human immunodeficiency virus (HIV) reported wanting children, but little is known about parenting desires of men who have sex with men (MSM) living with HIV. We examined parenting desires among persons initiating antiretroviral therapy (ART). METHODS: Of 1809 participants in the AIDS Clinical Trials Group (ACTG) Study 5257, 1425 W aged ≤45 years or men completed questionnaires about parenting desires at baseline and 96 weeks after initiating ART. Self-reported desires for children in the future (yes/unsure vs no) and associations between baseline sociodemographics and parenting desires at 96 weeks were examined using multivariable logistic regression, overall and within subgroups. RESULTS: The 1425 participants were as follows: 36% white, 39% black, 22% Hispanic; median age 36 (interquartile range, 28-44); 70% MSM, 13% men reported sex only with W (MSW), 17% W. At baseline, 42% may want children in the future (42% MSM, 37% MSW, 43% W); at 96 weeks, 41% may want children (41% MSM, 37% MSW, 43% W). At follow-up, approximately 10% of responses changed in each direction. In multivariable analyses, education greater than high school, <30 years, and having no children were significantly associated with future parenting desires among all subgroups. Among MSM, being black was associated with desiring children. CONCLUSIONS: Approximately 40% of MSM, W, and MSW with HIV may want children, both at baseline and 96 weeks after ART initiation. These results highlight the need to regularly assess parenting goals, provide access to comprehensive reproductive services, and address prevention of vertical and heterosexual HIV transmission.

Serum adipokine levels and associations with patient-reported fatigue in systemic lupus erythematosus.

Physical activity ameliorates fatigue in systemic lupus erythematosus (SLE) patients by an unknown mechanism. Adipokines, which are influenced by adiposity and physical activity, may be associated with patient-reported fatigue. We describe cross-sectional associations between adipokines and fatigue, physical activity, and SLE disease activity. We measured adipokines, self-reported fatigue, and objective physical activity in 129 SLE patients. Fatigue was assessed with the Fatigue Severity Scale (FSS) and Patient Reported Outcomes Measurement Information System® (PROMIS®) Fatigue score. Disease activity was measured with the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI). Participants wore an accelerometer for 7 days to measure physical activity. Leptin, adiponectin, and resistin were measured in stored serum with a Luminex bead-based assay. Multivariable regression models assessed relationships between fatigue and adipokines, and Spearman correlation coefficients summarized associations between adipokines, physical activity, and SELENA-SLEDAI. Median adipokine levels were: leptin 30.5 ng/ml (Interquartile Range 14.0, 56.6), adiponectin 11.6 µg/ml (7.2, 16.8) and resistin 1.4 ng/ml (1.0, 2.2). Associations between adipokines and FSS or PROMIS fatigue were not significant. Body mass index (BMI) ≥ 30 kg/m2 was associated with FSS and PROMIS fatigue in regression analyses (p < 0.05). Weak correlations between leptin, adiponectin, leptin/adiponectin (L/A) ratio, and physical activity and between adiponectin and SELENA-SLEDAI score were not significant after adjusting for BMI. Adipokines were not associated with fatigue in SLE. Adipokines were correlated with physical activity (leptin, adiponectin, L/A ratio) and SLE disease activity (adiponectin), but most of these associations were explained by BMI.

Varus Thrust and Incident and Progressive Knee Osteoarthritis.

OBJECTIVE: To determine if varus thrust, a bowing out of the knee during gait (i.e., the first appearance or worsening of varus alignment during stance), is associated with incident and progressive knee osteoarthritis (OA), we undertook an Osteoarthritis Initiative ancillary study. We further considered hypothesized associations adjusted for static alignment, anticipating some attenuation. METHODS: Gait was observed for the presence of thrust by 1 of 2-3 examiners per study site at 4 sites. In eligible knees, incident OA was defined as subsequent incident Kellgren/Lawrence grade ≥2, whole- and partial-grade medial joint space narrowing (JSN), and annualized loss of joint space width (JSW); progression was defined as medial JSN and JSW loss. Outcome measures were assessed for up to 7 years of follow-up. Analyses were knee-level, using multivariable logistic and linear regression with generalized estimating equations to account for between-limb correlation. RESULTS: The incident OA sample included 4,187 knees (2,610 persons); the progression sample included 3,421 knees (2,284 persons). In knees with OA, thrust was associated with progression as assessed by each outcome measure, with adjustment for age, sex, body mass index, and pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. In knees without OA, varus thrust was not associated with incident OA or other outcomes. After adjustment for alignment, the thrust-progression association was attenuated, but an independent association persisted for partial-grade JSN and JSW loss outcome models. WOMAC pain and alignment were consistently associated with all outcome measures. Within the stratum of varus knees, thrust was associated with an increased risk of progression. CONCLUSION: Varus thrust visualized during gait is associated with knee OA progression and should be a target of intervention development.

Incidence of Hepatitis C Virus Infection in the Human Immunodeficiency Virus Outpatient Study Cohort, 2000-2013.

BACKGROUND: There are few recent studies of incident hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected patients in the United States. METHODS: We studied HIV Outpatient Study (HOPS) participants seen in 9 HIV-specialty clinics who had ≥1 clinical encounter during 2000-2013 and ≥2 HCV-related tests, the first of which was a negative HCV antibody test (Ab). Hepatitis C virus incident cases were identified by first positive HCV Ab, viral load, or genotype. We assessed rates of incident HCV overall, by calendar intervals, and by demographic and HIV risk strata, and we explored risk factors for incident HCV using Cox proportional hazards models. RESULTS: The 1941 eligible patients (median age 40 years, 23% female, 61% men who had sex with men [MSM], and 3% persons who injected drugs [PWID]) experienced 102 (5.3%) incident HCV infections for an overall incidence of 1.07 (95% confidence interval [CI], 0.87-1.30) per 100 person-years (py). Hepatitis C virus incidence decreased from 1.83 in 2000-2003 to 0.88 in 2011-2013 (P = .024), with decreases observed (P < .05) among PWID and heterosexuals, but not among MSM. Overall, MSM comprised 59% of incident cases, and PWID were at most risk for incident HCV infection (adjusted hazard ratio [aHR] for PWID = 4.62 and 95% CI = 2.11-10.13; for MSM, aHR = 1.48 and 95% CI = 0.86-2.55 compared with heterosexuals). CONCLUSIONS: Among HIV-infected patients in care during 2000-2013, incidence of HCV infection exceeded 1 case per 100 py. Our findings support recommendations for annual HCV screenings for HIV-infected persons, including persons with only MSM risk, to enable HCV diagnosis and treatment for coinfected individuals.

Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients.

OBJECTIVE: To evaluate if molecular markers of eosinophilia in olfactory-enriched mucosa are associated with olfactory dysfunction. STUDY DESIGN: Cross-sectional study of tissue biopsies from 99 patients, and an additional 30 patients who underwent prospective olfactory testing prior to sinonasal procedures. METHODS: Tissue biopsies were processed for analysis of inflammatory markers using quantitative real time polymerase chain reaction (qRT-PCR). Ipsilateral olfactory performance was assessed using the Sniffin' Sticks (Burghart, Wedel, Germany) threshold component and the University of Pennsylvania Smell Identification Test (Sensonics, Haddon Heights, NJ). Age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from computed tomography and endoscopy. RESULTS: Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) compared to ST and inferior turbinate tissue in CRS without nasal polyps (CRSsNP) and control patients (all P < 0.001, respectively). CLC in ST tissue was correlated with IL-5 and eotaxin-1 expression (all P < 0.001; P = 0.65, and 0.49, respectively). CLC expression was strongly correlated with eosinophilic cationic protein levels (P < 0.001; r = -0.76), and ST CLC expression was inversely related to olfactory threshold (P = 0.002, r = -0.57) and discrimination scores (P = 0.05, r = -0.42). In multiple linear regression of CLC gene expression, polyp status, and radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (P < 0.05). CONCLUSION: Markers of eosinophils are elevated in the ST of patients with CRSwNP and correlate with olfactory loss. These findings support the hypothesis that olfactory dysfunction in CRS correlates local eosinophil influx into the olfactory cleft. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2210-2218, 2017.

Cardiovascular Disease Risk Prediction in the HIV Outpatient Study.

BACKGROUND: Cardiovascular disease (CVD) risk prediction tools are often applied to populations beyond those in which they were designed when validated tools for specific subpopulations are unavailable. METHODS: Using data from 2283 human immunodeficiency virus (HIV)-infected adults aged ≥18 years, who were active in the HIV Outpatient Study (HOPS), we assessed performance of 3 commonly used CVD prediction models developed for general populations: Framingham general cardiovascular Risk Score (FRS), American College of Cardiology/American Heart Association Pooled Cohort equations (PCEs), and Systematic COronary Risk Evaluation (SCORE) high-risk equation, and 1 model developed in HIV-infected persons: the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation. C-statistics assessed model discrimination and the ratio of expected to observed events (E/O) and Hosmer-Lemeshow χ2 P value assessed calibration. RESULTS: From January 2002 through September 2013, 195 (8.5%) HOPS participants experienced an incident CVD event in 15 056 person-years. The FRS demonstrated moderate discrimination and was well calibrated (C-statistic: 0.66, E/O: 1.01, P = .89). The PCE and D:A:D risk equations demonstrated good discrimination but were less well calibrated (C-statistics: 0.71 and 0.72 and E/O: 0.88 and 0.80, respectively; P < .001 for both), whereas SCORE performed poorly (C-statistic: 0.59, E/O: 1.72; P = .48). CONCLUSIONS: Only the FRS accurately estimated risk of CVD events, while PCE and D:A:D underestimated risk. Although these models could potentially be used to rank US HIV-infected individuals at higher or lower risk for CVD, the models may fail to identify substantial numbers of HIV-infected persons with elevated CVD risk who could potentially benefit from additional medical treatment.

Antiretroviral Regimen Durability and Success in Treatment-Naive and Treatment-Experienced Patients by Year of Treatment Initiation, United States, 1996-2011.

BACKGROUND: Although modern combination antiretroviral therapy (cART) regimens are better tolerated and less complex than earlier treatments, regimen modification or discontinuation remains a concern. METHODS: We studied HIV Outpatient Study (HOPS) participants who initiated the first or second cART regimens during: 1996-1999, 2000-2003, 2004-2007, and 2008-2011. We analyzed regimen durability (time to regimen modification) and success (achieving undetectable plasma HIV RNA) for the first and second cART regimens using Kaplan-Meier curves and log-rank tests, and examined factors associated with durability and success of the first cART regimen using proportional hazards models. RESULTS: Durability of cART was progressively longer for cART regimens initiated in more recent periods: median first cART regimen durations were 1.0, 1.1, 2.1, and 4.6 years in 1996-1999, 2000-2003, 2004-2007, and 2008-2011, and the median second cART durations were 0.9, 1.2, 2.8, and 3.9 years, respectively (both P < 0.001). Comparing 1996-1999 and 2008-2011, the percentage of patients who achieved an undetectable HIV RNA within 6 months of first cART initiation increased from 65% to 81% and from 63% to 80% on second cART (both P < 0.001). Among patients initiating first cART during 2008-2011, black non-Hispanic/Latino race/ethnicity and ≥ twice-daily dosing were significantly associated with higher rates of regimen modification (P < 0.05), and higher baseline HIV RNA levels were associated with failure to achieve an undetectable HIV RNA (P < 0.001). CONCLUSIONS: Among HIV-infected U.S. adults in routine HIV care, durability of the first and second cART regimens and the likelihood of prompt virological suppression increased during 1996-2011, coincident with the availability of more tolerable, less complex cART options.