Explore the vast range of titles available.

HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors. Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m²; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)]. HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.

The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation.

Among persons with HIV (PWH), unhealthy alcohol use and polypharmacy contribute to bothersome symptoms (e.g., fatigue, dizziness, memory loss). However, effective risk communication targeting these associations is challenging. The HIV and Alcohol Research center focused on Polypharmacy (HARP) is conducting a pilot study that will generate feasibility and acceptability data on a clinical pharmacist-delivered counseling intervention targeting the modification of unhealthy alcohol use and polypharmacy in PWH. Counseling is guided by the Information-Motivation-Behavioral Skills-Motivational Interviewing (IMB-MI) model. Herein, we describe the study protocol. This pilot uses a one-group pre-test/post-test design. We will recruit 50 participants from those who participated in the consented cohort of the Veterans Aging Cohort Study. Participants must be prescribed  ≥  5 long-term medications, have a self-reported Alcohol Use Disorders Identification Test score > 0, and be living with HIV. We will exclude those with moderate-severe alcohol use disorder as identified by an Alcohol Symptom Checklist score  ≥  4. Data are collected using three self-administered surveys (baseline, immediately after booster intervention, and 30-days post-intervention), two PEth blood tests (baseline, 30 days post-intervention), and medication data from the electronic health record (baseline). The intervention includes a 60-minute IMB-MI-based counseling session followed by a booster session 2 weeks later. Some participants will also be asked to participate in a qualitative interview to provide feedback on the intervention. The pilot investigates the impact of an intervention on alcohol consumption and the use of multiple medications among PWH, exploring how best to reduce bothersome symptoms, communicate risk, and support behavior change in this population.

This study aimed to evaluate treatment necessity, treatment concern, and willingness to engage in decisional trade-offs in the context of treatment escalation decision-making. Participants (n = 147) recruited online were randomized to read a vignette about escalating care in psoriasis in a 2 (high treatment concern vs moderate treatment concern) × 2 (high perceived treatment necessity vs moderate perceived treatment necessity) design. High treatment concern was associated with choosing to defer treatment escalation and being unwilling to engage in decisional trade-offs if disease risk changed. Results highlight the importance of treatment concern and willingness trade-off in treatment escalation decision-making.

Objective We aim to describe an evidence synthesis approach using parallel streams of evidence that informed the development of the 2021 American College of Rheumatology (ACR) guideline for the management of rheumatoid arthritis (RA). Methods We developed the evidence synthesis approach using parallel streams of evidence in multiple rounds of discussion, piloting, feedback, and revisions. A number of working groups involving ACR staff, content experts, and methodologists coordinated to develop and implement the approach. Results We used a major stream of evidence that identified evidence specific to the clinical questions being addressed in the guideline (ie, we were able to match relevant articles to specific questions). We also used additional streams that identified data that applied across multiple questions. We describe in this article the different steps of the major stream, ie, screening and tagging, matching articles to question clusters, matching articles to individual questions, data ion and analysis, and Grading of Recommendations Assessment, Development and Evaluation (GRADEing). We then describe how we packaged the parallel streams of evidence into standardized structured tables to facilitate formulating the recommendations. These tables included information for the following factors: desirable effects, undesirable effects, certainty of evidence, valuation of outcomes, cost of interventions, and cost‐effectiveness of interventions. The approach allowed us to match eligible articles for 47 of 81 clinical questions. We identified no eligible articles that addressed the remaining 34 questions. Conclusion We were successful in using parallel streams of evidence to inform the development of the 2021 ACR guideline for the management of RA.

Abstract BackgroundCase reports describe incident sarcoidosis in persons with HIV (PWH). The association between HIV and risk of sarcoidosis, and differences in presentation in PWH, have not been systematically assessed. MethodsSubjects were selected from the Veterans Aging Cohort Study (VACS), a longitudinal cohort study including veterans with HIV and matched uninfected veterans. This was a prospective observational analysis in which we evaluated both the incidence (via incidence rate ratio) and presentation and treatment (by comparison of rates of organ involvement and use of medications) of sarcoidosis in PWH compared with HIV-negative controls. We also assessed risk factors (via Cox regression) associated with the development of sarcoidosis including CD4 count and viral load trajectory. ResultsOf 1614 patients evaluated via chart review, 875 (54%) had prevalent sarcoidosis and 325 (20%) had confirmed incident sarcoidosis. Incident sarcoidosis occurred in 59 PWH and 266 uninfected. The incidence of sarcoidosis was lower in PWH than uninfected (incidence rate ratio [IRR], 0.61; 95% CI, 0.46–0.81) and especially low in patients with unsuppressed viremia (IRR, 0.04; 95% CI, 0.02–0.08) compared with uninfected). At diagnosis of sarcoidosis, the median CD4 count among PWH was 409 cells/mm3; 77% had HIV-1 RNA <500 copies/mL. No significant differences were observed between PWH and uninfected in terms of organ involvement, disease severity, or use of oral glucocorticoids. ConclusionsHIV, particularly with persistent viremia, was associated with decreased risk of incident sarcoidosis; severity and treatment were similar between PWH and uninfected.