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The nitrogen is doped during the sputter deposition of the recording material and GeN nucleation-promotion layers are inserted above and below the recording layer in order to enhance the data transfer rate of eutectic Sb-Te phase-change optical disk. Transmission electron microscopy has disclosed that nitrogen doping is able to promote the phase transformation by generating many nucleation sites uniformly distributed in the recording layer.

This work prepared the highly transparent photo‐curable co‐polyacrylate/silica nanocomposites by using sol‐gel process. The FTIR and 13C NMR analyses indicated that during the sol‐gel process, the hybrid precursors transform into composites containing nanometer‐scale silica particles and crosslinked esters/anhydrides. Transmission electron microscopy (TEM) revealed that the silica particles within the average size of 11.5 nm uniformly distributed in the nanocomposite specimen containing about 10 wt % of Si. The nanocomposite specimens exhibited satisfactory thermal stability that they had 5% weight loss decomposition temperatures higher than 150°C and coefficient of thermal expansion (CTE) less than 35 ppm/°C. Analysis via derivative thermogravimetry (DTG) indicated that the crosslinked esters/anhydrides might influence the thermal stability of nanocomposite samples. The UV‐visible spectroscopy indicated that the nanocomposite resins possess transmittance higher than 80% in visible light region. Permeability test revealed a higher moisture permeation resistance for nanocomposite samples, which indicated that the implantation of nano‐scale silica particles in polymer matrix forms effective barrier to moisture penetration. Adhesion test of nanocomposite samples on glass substrate showed at least twofold improvement of adhesion strength compared with oligomer. This evidenced that the silica and the hydrophilic segments in nanocomposite resins might form interchains hydrogen bonds with the —OH groups on the surface of glass so the substantial enhancement of adhesion strength could be achieved. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007 [ABSTRACT FROM AUTHOR]

In this paper, we perform a systematic evaluation of the impact of Global Positioning System radio occultation (GPSRO) data on typhoon-track prediction over the northwestern Pacific. Specifically, we perform data assimilation and forecast experiments using the Typhoon Weather Research and Forecasting (TWRF) system at 45 km resolution on 11 typhoons (with a total of 327 cases) in the period of 2008–2010 over the northwestern Pacific, with or without the use of GPSRO refractivity observations. On average, about 100 GPSRO soundings are assimilated over a 12 h partially cycling assimilation period. The results indicate that the assimilation of GPSRO data reduces the 72 h track forecast errors by approximately 12 km (5 %). Although this is only a modest improvement, it is statistically significant. The assimilation of GPSRO data improves the analysis and the forecast of temperature, water vapor, and wind fields. Further analysis shows that the reduction in typhoon-track forecast errors can be attributed to the improved prediction of western Pacific subtropical high (WPSH) and its associated circulation, which leads to better forecasting of the environmental steering flow.

In the ACC/AHA guidelines, the presence of symptoms plays a central role in determining timing surgery in primary mitral regurgitation (MR). Studies have shown a disconnect between the severity of MR and symptoms. The purpose of this study is to assess risk factors for symptoms in patients with chronic primary MR. There were 430 patients with degenerative MR and preserved left ventricular function who underwent cardiovascular magnetic resonance (CMR). MR volume (MRV) and MR fraction (MRF) were categorized as per the ACC/AHA guidelines. Patients were divided into three groups based on category of MRV and MRF: (1) MRV category > MRF category (V > F), (2) MRV = MRF category (V = F), and (3) MRV < MRF category (V < F). Symptoms were defined as shortness of breath, fatigue, and decreased exercise capacity and extracted from chart review. There were 134 (38%) patients who reported symptoms. Based on MRV, 236 (55%), 125 (29%), and 69 (16%) patients had mild moderate, and severe MR respectively. Based on MRF, 257 (60%), 130 (30%), and 43 (10%) patients had mild moderate, and severe MR respectively. There was no increase in the prevalence of symptoms with worsening MRV severity (39%, 40% and 30% for mild, moderate and severe MRV respectively, p = 0.4). There was a trend for increase in the prevalence of symptoms in patients with severe MRF (35%, 40% and 54% for mild, moderate and severe MRF respectively, p = 0.054). There was a significant increase in the prevalence of symptoms when comparing V > F, V = F, and V < F (20%, 40%, and 72% respectively, p < 0.0001). On multivariable analysis, risk factors for symptoms were age, female sex, MRF, and having a V < F. In patients undergoing CMR with degenerative MR the prevalence of symptoms do not increase with worsening MRV. MRV and MRF were not risk factors for symptoms but having V < F was a risk factors for the presence of symptoms. These findings suggest that symptomatic patients with MR may have other pathology which may be responsible for their symptoms. Further studies are needed to better characterize the relationship between MR severity and symptoms., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval, consent to participate, and consent to publish: This was an observational retrospective study. The hospital’s Institutional Review Board (IRB) approved the present study and waived informed consent. All authors read and approved the final manuscript for publication., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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., Competing Interests: Declarations. Competing Interests: None of the other authors report competing interests. ClinicalTrials.gov Identifier: NCT05560932., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The ways that families communicate about traumatic experiences is a critical social process. Intrafamily trauma communication encompasses approaches through which family members share and respond to difficult past experiences. We examined the embedded communication processes and actions of war-affected Karen maternal caregivers living post-resettlement in the United States, as they described disclosures of torture and war trauma experiences to their children. Using a modified approach to a constructivist-oriented grounded theory, we analyzed 33 in-depth qualitative interviews. Narrative experiences of mothers and synthesized storylines shaped a psychosocial theory of maternal intrafamily trauma communication, Ushering a Witness . The core category was depicted by the coalescence of three distinct conceptual, temporal phases and corresponding properties: (a) Appraising: Communication decision-making, (b) (Co-)Constructing: Act of communicating, and (c) Amending: Developing awareness and reevaluating purpose, response, and approach to communication. Findings will facilitate further exploration of the relationships between the intergenerational effects of trauma and intergenerational communication., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We propose a theoretical framework that identifies (a) the different categories of stakeholders and (b) the normative values that drive their attitudes toward direct-to-consumer genetic testing, with an emphasis on the reproductive health contexts. We conducted a literature search using varied combinations of search terms, including direct-to-consumer genetic testing, decision-making, reproductive health, and policy. Using a grounded theory approach to existing literature and in combination with a narrative review, we present a systematic framework of five categories of stakeholders (i.e., genome-driven stakeholders, industry-driven stakeholders, history-driven stakeholders, value-driven stakeholders, and social justice-driven stakeholders) that shape the public's discourse. Moving beyond the dialectical ethics that have governed the public discourse, we also identify the normative values and interests that motivate different stakeholders' attitudes and decision-making through theoretical sampling under the grounded theory. We investigate the competing and conflicting values within the same category of stakeholders. For example, despite being industry-driven stakeholders, medical professionals' attitudes are driven by concerns about standards of care; in contrast, health insurance companies' concerns are centered on profit. We further explore the tensions between these stakeholders that impact their strategic alliances and pose challenges to the practices of direct-to-consumer genetic testing. Finally, we examine how these stakeholders and their corresponding values may shape future development and policies of direct-to-consumer genetic testing in the context of reproductive health.

Research regarding HIV, substance use disorders (SUD), and SARS-CoV-2 infections after COVID-19 vaccination is limited. In the Veterans Aging Cohort Study (VACS)-HIV cohort, we followed vaccinated persons with HIV (PWH) and without HIV (PWoH) from 12/2020 to 3/2022 and linked SARS-CoV-2 test results for laboratory-confirmed breakthrough infection through 9/2022. We examined associations of substance use (alcohol use disorder [AUD], other SUD, smoking status) and HIV status and severity with breakthrough infections, using Cox proportional hazards regression hazard ratios (HR). To test for potential interactions between substance use and HIV, we fit survival models with a multiplicative interaction term. Among 24,253 PWH and 53,661 PWoH, 8.0% of PWH and 7.1% of PWoH experienced COVID-19 breakthrough. AUD (HR 1.42, 95% CI 1.32, 1.52) and other SUD (HR 1.49, 95% CI 1.39, 1.59) were associated with increased risk of breakthrough, and this was similar by HIV status (p-interaction > 0.09). Smoking was not associated with breakthrough. Compared to PWoH, PWH at all HIV severity levels had increased risk of breakthrough ranging from 9% for PWH with CD4 count ≥ 500 cells/µl (HR 1.09, 95% CI 1.02, 1.17) to 59% for PWH with CD4 count < 200 (HR 1.59, 95% CI 1.31, 1.92). Patients with AUD (HR 1.42, 95% CI 1.33, 1.52) and other SUD (HR 1.48, 95% CI 1.38, 1.59) had increased COVID-19 breakthrough risk, regardless of HIV status. HIV was associated with breakthrough; risk was greatest among PWH with lower CD4 count. In addition to inhibiting HIV treatment adherence and increasing HIV progression, AUD and other SUD may increase COVID-19 breakthrough risk., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Inflammation is a significant contributor to cardiovascular disease (CVD) in people with HIV (PWH), who face twice the risk of CVD compared to the general population. The presence of co-existing rheumatic disease (RD) may further exacerbate inflammation and increase the incidence of CVD events in this population. Methods : We conducted a retrospective cohort study using electronic health record (EHR) data from the Veterans Affairs Medical Center in Atlanta, covering the period from 2000 to 2019. A total of 5000 patients aged 20-87 years who were diagnosed with HIV and receiving care at the Atlanta VAMC between 2000 and 2019 were eligible for this analysis. This study included 3930 veterans with HIV and assessed the impact of rheumatic disease therapies (RDTs) on CVD outcomes. The primary outcome was the first occurrence of a CVD event. Results: Rheumatic disease was significantly associated with an increased risk of CVD events (OR = 2.67; p < 0.001). Additionally, exposure to multiple RDTs (aHR = 2.121, p = 0.047), NSAIDs (aHR = 1.694, p = 0.003), glucocorticoids (aHR = 2.332, p < 0.0001), and hypouricemic agents and colchicine (aHR = 3.445, p < 0.0001) were all significantly associated with increased CVD events. Conclusions: The co-existence of HIV infection and rheumatic disease, along with the use of RDTs, may amplify the risk of CVD events in PWH. These findings underscore the need for further investigation into the relationship between RD, RDTs, and CVD risk in larger, controlled studies, given the potential implications for treatment decisions in this patient population. A limitation of our study is that due to its retrospective design, we could not examine the impact of the sequential use of RDT groups and RD severity on CVD events.

Objective: To develop and test an NLP algorithm that accurately detects the presence of information reported from DXA scans containing femoral neck T-scores of the patients scanned. Methods: A rule-based NLP algorithm that iteratively built a collection of regular expressions in testing data consisting of 889 snippets of text pulled from DXA reports. This was manually checked by clinical experts to determine the proportion of manually verified annotations that contained T-score information detected by this algorithm called 'BoneScore'. Testing of 30- and 50-word lengths on each side of the key term 'femoral' were pursued until achievement of adequate accuracy. A separate clinical validation regressed the extracted T-score values on five risk factors with established associations. Results: BoneScore built a set of 20 regular expressions that in concert with a width of 50 words on each side of the key term yielded an accuracy of 98% in the testing data. The extracted T-scores, when modeled with multivariable linear regression, consistently exhibited associations supported by the literature. Conclusion: BoneScore uses regular expressions to accurately extract annotations of T-score values of bone mineral density with a width of 50 words on each side of the key term. The extracted T-scores exhibit clinical face validity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The latent HIV reservoir is a major barrier to HIV cure. Combining latency reversal agents (LRAs) with differing mechanisms of action such as AZD5582, a non-canonical NF-kB activator, and I-BET151, a bromodomain inhibitor is appealing towards inducing HIV-1 reactivation. However, even this LRA combination needs improvement as it is inefficient at activating proviruses in cells from people living with HIV (PLWH). We performed a CRISPR screen in conjunction with AZD5582 & I-BET151 and identified a member of the Integrator complex as a target to improve this LRA combination, specifically Integrator complex subunit 12 (INTS12). Integrator functions as a genome-wide attenuator of transcription that acts on elongation through its RNA cleavage and phosphatase modules. Knockout of INTS12 improved latency reactivation at the transcriptional level and is more specific to the HIV-1 provirus than AZD5582 & I-BET151 treatment alone. We found that INTS12 is present on chromatin at the promoter of HIV and therefore its effect on HIV may be direct. Additionally, we observed more RNAPII in the gene body of HIV only with the combination of INTS12 knockout with AZD5582 & I-BET151, indicating that INTS12 induces a transcriptional elongation block to viral reactivation. Moreover, knockout of INTS12 increased HIV-1 reactivation in CD4 T cells from virally suppressed PLWH ex vivo . We also detected viral RNA in the supernatant from CD4 T cells of all three virally suppressed PLWH tested upon INTS12 knockout suggesting that INTS12 prevents full-length HIV RNA production in primary T cells., Competing Interests: Competing interest statement The authors declare they have no competing interests.

Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE., Methods: This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6 months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected., Results: Thirteen patients with active major NPSLE, 13 age/sex/kidney function matched SLE controls without active major NPSLE, and 13 age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6 years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3 pg/ml ( p = .42) and 1.2 pg/ml higher ( p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2 pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy., Conclusions: Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species 1 . Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe 1,2 . To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia 3 . Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago., (© 2024. The Author(s).)

Although the public health emergency associated with the COVID-19 pandemic has ended, challenges remain, especially for individuals with rheumatic diseases. We aimed to assess the historical and ongoing effects of COVID-19 on individuals with rheumatic diseases and rheumatology practices globally, with specific attention to vulnerable communities and lessons learned. We reviewed literature from several countries and regions, including Africa, Australia and New Zealand, China, Europe, Latin America, and the US. In this review, we summarize literature that not only examines the impact of the pandemic on individuals with rheumatic diseases, but also research that reports the lasting changes to rheumatology patient care and practice, and health service use. Across countries, challenges faced by individuals with rheumatic diseases during the pandemic included disruptions in health care and medication supply shortages. These challenges were associated with worse disease and mental health outcomes in some studies, particularly among those who had social vulnerabilities defined by socioeconomic, race, or rurality. Moreover, rheumatology practice was impacted in all regions, with the uptake of telemedicine and changes in health care utilization. While many regions developed rapid guidelines to disseminate scientific information, misinformation and disinformation remained widespread. Finally, vaccine uptake among individuals with rheumatic diseases has been uneven across the world. As the acute phase of the pandemic wanes, ongoing efforts are needed to improve health care access, stabilize rheumatology drug supplies, improve public health communication, and implement evidence-based vaccination practices to reduce COVID-19 morbidity and mortality among individuals with rheumatic diseases., (© 2023 American College of Rheumatology.)

Background: Implementing effective self-care practices for non-communicable diseases (NCD) prevents complications and morbidity. However, scanty evidence exists among patients in rural sub-Saharan Africa (SSA). We sought to describe and compare existing self-care practices among patients with hypertension (HTN) and diabetes (DM) in rural Uganda., Methods: Between April and August 2019, we executed a cross-sectional investigation involving 385 adult patients diagnosed with HTN and/or DM. These participants were systematically randomly selected from three outpatient NCD clinics in the Nakaseke district. Data collection was facilitated using a structured survey that inquired about participants' healthcare-seeking patterns, access to self-care services, education on self-care, medication compliance, and overall health-related quality of life. We utilized Chi-square tests and logistic regression analyses to discern disparities in self-care practices, education, and healthcare-seeking actions based on the patient's conditions., Results: Of the 385 participants, 39.2% had only DM, 36.9% had only HTN, and 23.9% had both conditions (HTN/DM). Participants with DM or both conditions reported more clinic visits in the past year than those with only HTN (P = 0.005). Similarly, most DM-only and HTN/DM participants monitored their weight monthly, unlike those with only HTN (P<0.0001). Participants with DM or HTN/DM were more frequently educated about their health condition(s), dietary habits, and weight management than those with only HTN. Specifically, education about their conditions yielded adjusted odds ratios (aOR) of 5.57 for DM-only and 4.12 for HTN/DM. Similarly, for diet, aORs were 2.77 (DM-only) and 4.21 (HTN/DM), and for weight management, aORs were 3.62 (DM-only) and 4.02 (HTN/DM). Medication adherence was notably higher in DM-only participants (aOR = 2.19). Challenges in self-care were significantly more reported by women (aOR = 2.07) and those above 65 years (aOR = 5.91), regardless of their specific condition(s)., Conclusion: Compared to rural Ugandans with HTN-only, participants with DM had greater utilization of healthcare services, exposure to self-care education, and adherence to medicine and self-monitoring behaviors. These findings should inform ongoing efforts to improve and integrate NCD service delivery in rural SSA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Importance: Despite the frequency of total knee arthroplasty (TKA) and clinical implications of prosthetic joint infections (PJIs), knowledge gaps remain concerning the incidence, microbiological study results, and factors associated with these infections., Objectives: To identify the incidence rates, organisms isolated from microbiological studies, and patient and surgical factors of PJI occurring early, delayed, and late after primary TKA., Design, Setting, and Participants: This cohort study obtained data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse on patients who underwent elective primary TKA in the VA system between October 1, 1999, and September 30, 2019, and had at least 1 year of care in the VA prior to TKA. Patients who met these criteria were included in the overall cohort, and patients with linked Veterans Affairs Surgical Quality Improvement Program (VASQIP) data composed the VASQIP cohort. Data were analyzed between December 9, 2021, and September 18, 2023., Exposures: Primary TKA as well as demographic, clinical, and perioperative factors., Main Outcomes and Measures: Incident hospitalization with early, delayed, or late PJI. Incidence rate (events per 10 000 person-months) was measured in 3 postoperative periods: early (≤3 months), delayed (between >3 and ≤12 months), and late (>12 months). Unadjusted Poisson regression was used to estimate incidence rate ratios (IRRs) with 95% CIs of early and delayed PJI compared with late PJI. The frequency of organisms isolated from synovial or operative tissue culture results of PJIs during each postoperative period was identified. A piecewise exponential parametric survival model was used to estimate IRRs with 95% CIs associated with demographic and clinical factors in each postoperative period., Results: The 79 367 patients (median (IQR) age of 65 (60-71) years) in the overall cohort who underwent primary TKA included 75 274 males (94.8%). A total of 1599 PJIs (2.0%) were identified. The incidence rate of PJI was higher in the early (26.8 [95% CI, 24.8-29.0] events per 10 000 person-months; IRR, 20.7 [95% CI, 18.5-23.1]) and delayed periods (5.4 [95% CI, 4.9-6.0] events per 10 000 person-months; IRR, 4.2 [95% CI, 3.7-4.8]) vs the late postoperative period (1.3 events per 10 000 person-months). Staphylococcus aureus was the most common organism isolated overall (489 [33.2%]); however, gram-negative infections were isolated in 15.4% (86) of early PJIs. In multivariable analyses, hepatitis C virus infection, peripheral artery disease, and autoimmune inflammatory arthritis were associated with PJI across all postoperative periods. Diabetes, chronic kidney disease, and obesity (body mass index of ≥30) were not associated factors. Other period-specific factors were identified., Conclusions and Relevance: This cohort study found that incidence rates of PJIs were higher in the early and delayed vs late post-TKA period; there were differences in microbiological cultures and factors associated with each postoperative period. These findings have implications for postoperative antibiotic use, stratification of PJI risk according to postoperative time, and PJI risk factor modification.

Outcomes for post-chimeric antigen receptor (CAR) T cell therapy (CART) relapse are poor. The utilization of a unique CAR T cell construct for post-CART failure is increasing, but this approach is not well described. In this study, with CART-A the first unique CAR T cell construct received and CART-B the second, the primary objective was to characterize outcomes following CART-B. Secondary objectives included evaluating safety and toxicity with sequential CART infusions; investigating the impact of potential factors, such as antigen modulation and interval therapy, on CART-B response; and characterizing long-term outcomes in patients receiving multiple CARTs. This was a retrospective review (NCT03827343) of children and young adults with B cell acute lymphoblastic leukemia (B-ALL) undergoing CART therapy who received at least 2 unique CART constructs, excluding interim CART reinfusions of the same product. Of 135 patients, 61 (45.1%) received 2 unique CART constructs, including 13 who received >2 CARTs over time. Patients included in this analysis received 14 distinct CARTs targeting CD19 and/or CD22. The median age at CART-A was 12.6 years (range, 3.3 to 30.4 years). The median time from CART-A to CART-B was 302 days (range, 53 to 1183 days). CART-B targeted a different antigen than CART-A in 48 patients (78.7%), owing primarily to loss of CART-A antigen target. The rate of complete remission (CR) was lower with CART-B (65.5%; 40 of 61) than with CART-A (88.5%; 54 of 61; P = .0043); 35 of 40 (87.5%) CART-B responders had CART-B targeting a different antigen than CART-A. Among the 21 patients with a partial response or nonresponse to CART-B, 8 (38.1%) received CART-B with the same antigen target as CART-A. Of 40 patients with CART-B complete response (CR), 29 (72.5%) relapsed. For the 21 patients with evaluable data, the relapse immunophenotype was antigen negative in 3 (14.3%), antigen dim in 7 (33.3%), antigen positive in 10 (47.6%), and lineage switch in 1 (4.8%). The median relapse-free survival following CART-B CR was 9.4 months (95% confidence interval [CI], 6.1 to 13.2 months), and overall survival was 15.0 months (95% CI, 13.0 to 22.7 months). Given the limited salvage options for post-CART relapse, identifying optimizing strategies for CART-B is critical. We raise awareness about the emerging use of CART for post-CART failure and highlight clinical implications accompanying this paradigm shift., (Published by Elsevier Inc.)

Management of chronic conditions and optimization of overall health has become a primary global health concern in the care of people living with HIV in the era of highly active antiretroviral therapy (ART), particularly in lower-and-middle income countries where infrastructure for chronic disease management may be fragmented. Alterations in body composition can reflect important changes in musculoskeletal health, particularly among populations at risk for developing fat and muscle redistribution syndromes, such as women with HIV on ART. Given the lack of data on this topic in Latin America and the Caribbean, we designed an exploratory study to measure these outcomes in a population of women aging with HIV in Peru. We conducted a cross-sectional study among Peruvian women with and without HIV aged ≥40 years. Dual X-ray absorptiometry was used to measure trunk and limb lean mass (LM) and fat mass (FM). Physical performance was assessed with the Short Physical Performance Battery (SPPB) and physical strength with a dynamometer. Sarcopenia was assessed based upon EWGSOP criteria. We used linear regression to model associations between body composition, sarcopenia and physical performance scores. 104 women with HIV and 212 women without HIV were enrolled (mean age 52.4±8.2 vs. 56.4±8.8 years, p≤0.001). Among women with HIV, mean years since diagnosis was 11.8±6 and all were on ART. Mean SPPB score was 9.9 vs 10.8 (p<0.001) between both groups. Sarcopenia spectrum was found in 25.9% and 23.1%, respectively. In the multivariable regression analysis, trunk FM and older age were negatively correlated with physical performance among women with HIV. Severe sarcopenia was found among a greater proportion of those with HIV (3.8% vs. 0.9%, p = 0.84), however this finding was not statistically significant. Women with HIV had significantly lower SPPB scores compared to women without HIV, and trunk FM and upper limb LM were independent predictors for the SPPB and Grip Strength tests, respectively. Larger, prospective studies are needed in Latin America & the Caribbean to identify individuals at high risk for sarcopenia and declines in physical function, and to inform prevention guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cabrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Fragility fractures (fractures) are a critical outcome for persons aging with HIV (PAH). Research suggests that the fracture risk assessment tool (FRAX) only modestly estimates fracture risk among PAH. We provide an updated evaluation of how well a 'modified FRAX' identifies PAH at risk for fractures in a contemporary HIV cohort., Design: Cohort study., Methods: We used data from the Veterans Aging Cohort Study to evaluate veterans living with HIV, aged 50+ years, for the occurrence of fractures from 1 January 2010 through 31 December 2019. Data from 2009 were used to evaluate the eight FRAX predictors available to us: age, sex, BMI, history of previous fracture, glucocorticoid use, rheumatoid arthritis, alcohol use, and smoking status. These predictor values were then used to estimate participant risk for each of two types of fractures (major osteoporotic and hip) over the subsequent 10 years in strata defined by race/ethnicity using multivariable logistic regression., Results: Discrimination for major osteoporotic fracture was modest [Blacks: area under the curve (AUC) 0.62; 95% confidence interval (CI) 0.62, 0.63; Whites: AUC 0.61; 95% CI 0.60, 0.61; Hispanic: AUC 0.63; 95% CI 0.62, 0.65]. For hip fractures, discrimination was modest to good (Blacks: AUC 0.70; 95% CI 0.69, 0.71; Whites: AUC 0.68; 95% CI 0.67, 0.69]. Calibration was good in all models across all racial/ethnic groups., Conclusion: Our 'modified FRAX' exhibited modest discrimination for predicting major osteoporotic fracture and slightly better discrimination for hip fracture. Future studies should explore whether augmentation of this subset of FRAX predictors results in enhanced prediction of fractures among PAH., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown., Methods: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within the past 12 months, body mass index, physiologic frailty (VACS Index 2.0), illicit substance and alcohol use disorders, and measures of multimorbidity and polypharmacy. We separately fit multivariable logistic models to each outcome using generalized estimating equations. From these models, the longitudinal extensions of average attributable fraction (LE-AAF) for modifiable risk factors were estimated., Results: Key risk factors for both outcomes included physiologic frailty (VACS Index 2.0) (serious falls [15%; 95% CI 14%-15%]; fractures [13%; 95% CI 12%-14%]), a serious fall in the past year (serious falls [7%; 95% CI 7%-7%]; fractures [5%; 95% CI 4%-5%]), polypharmacy (serious falls [5%; 95% CI 4%-5%]; fractures [5%; 95% CI 4%-5%]), an opioid prescription in the past month (serious falls [7%; 95% CI 6%-7%]; fractures [9%; 95% CI 8%-9%]), and diagnosis of alcohol use disorder (serious falls [4%; 95% CI 4%-5%]; fractures [8%; 95% CI 7%-8%])., Conclusions: This study confirms the contributions of risk factors important in the general population to both serious falls and fragility fractures among older PWH. Successful prevention programs for these outcomes should build on existing prevention efforts while including risk factors specific to PWH., (© 2023 The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Osteoporosis and fracture risk among women with HIV in Latin America is understudied. In a sample of Peruvian women with and without HIV, women with HIV had lower femoral neck and total hip BMD and a higher proportion of vertebral fractures. Important treatment gaps were identified across both groups., Purpose: Studies have shown that patients with HIV are at increased risk for bone loss and fracture due to a combination of host, viral, and antiretroviral therapy (ART)-related factors. We aimed to explore the prevalence of vertebral fracture (VF) and low bone mineral density (BMD) among women aging with HIV in Peru and identify risk factors for osteoporosis and fracture in this population., Methods: We enrolled women living with and without HIV aged ≥40 years between 2019 and 2020. Participants completed a survey and obtained dual X-ray absorptiometry (DXA) test to assess BMD at the lumbar spine (LS), femoral neck (FN), and total hip (TH). A subset of patients also obtained lateral thoracolumbar X-rays. Presence of VF was determined using the Genant semiquantitative method. Regression analyses were used to model associations between key risk factors and BMD., Results: 104 women living with HIV and 212 women living without HIV were enrolled with a mean age of 52.4±8.2 and 56.4±8.8 years (p < 0.001). Among postmenopausal women (257/316, 81.3%), 26.3% of women living with HIV and 25.9% of those without HIV had osteoporosis. Among the 88 women living with HIV and 178 women living without HIV who obtained thoracolumbar X-rays, 12.5% and 6.2%, respectively, had at least one VF. Based on DXA and the FRAX score, 22/104 women living with HIV met criteria for osteoporosis treatment according to national guidelines; however, none were on treatment. Propensity score matching revealed that women living with HIV had 0.032 g/cm 2 lower FN BMD (p = 0.012) and 0.034 g/cm 2 lower TH BMD (p = 0.041) compared to women without HIV., Conclusion: In this study, women living with HIV on long-standing ART had increased VF prevalence compared to the slightly older group of women without HIV. Age and BMI were independent predictors for BMD at the lumbar spine, hip, and femoral neck among women living with HIV, and there was a treatment gap among women who met criteria for osteoporosis treatment. Larger studies are needed in this region to identify individuals at risk for fracture and to inform prevention guidelines., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objectives: To investigate the clinical features and factors associated with primary Sjögren's syndrome (pSS)-associated renal tubular acidosis (RTA)., Method: This case-control study was based on a multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients with pSS, including those with RTA and those without renal involvement, between May 2016 and March 2020 were included in the analysis. Demographic, clinical, and laboratory data were also collected. Univariate and multivariate logistic regression analyses were used to identify factors that were associated with pSS-RTA., Results: This study included 257 pSS patients with RTA and 4222 patients without renal involvement. Significantly younger age at disease onset (40.1 ± 14.1 vs. 46.2 ± 13.1 years, P < 0.001), longer diagnosis interval (15.0 interquartile range [IQR] [1.0, 48.0] vs. 6.0 IQR [0, 34.0] months, P < 0.001), higher EULAR Sjögren's syndrome disease activity index (9 IQR [5, 15] vs. 3 IQR [0, 8], P < 0.001), and a higher prevalence of decreased estimated glomerular filtration rate (25.0% vs. 6.6%, P < 0.001) were observed in pSS patients with RTA than in those without renal involvement. Factors that were independently associated with pSS-RTA included age at disease onset ≤ 35 years (odds ratio [OR] 3.00, 95% confidence interval [CI] 2.27-3.97), thyroid disorders (OR 1.49, 95% CI 1.04-2.14), subjective dry mouth (OR 3.29, 95% CI 1.71-6.35), arthritis (OR 1.57, 95% CI 1.10-2.25), anti-SSB antibody positivity (OR 1.80, 95% CI 1.33-2.45), anemia (OR 1.67, 95% CI 1.26-2.21), elevated alkaline phosphatase level (OR 2.14, 95% CI 1.26-3.65), decreased albumin level (OR 1.61, 95% CI 1.00-2.60), and elevated erythrocyte sedimentation rate (OR 1.78, 95% CI 1.16-2.73)., Conclusions: Delayed diagnosis and decreased kidney function are common in pSS patients with RTA. pSS should be considered in patients with RTA, and early recognition and treatment may be useful in slowing the deterioration of renal function in patients with pSS-RTA. Key Points • pSS patients with RTA have earlier disease onset and higher disease activity than pSS patients without RTA, but the diagnosis was frequently delayed. • Decreased kidney function are common in pSS patients with RTA. • Sjögren's syndrome should be considered in young female patients with unexplained RTA, whereas RTA should be screened in pSS patients with early disease onset and elevated ALP level., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Transcriptional silencing of latent HIV-1 proviruses entails complex and overlapping mechanisms that pose a major barrier to in vivo elimination of HIV-1. We developed a new latency CRISPR screening strategy, called Latency HIV-CRISPR which uses the packaging of guideRNA-encoding lentiviral vector genomes into the supernatant of budding virions as a direct readout of factors involved in the maintenance of HIV-1 latency. We developed a custom guideRNA library targeting epigenetic regulatory genes and paired the screen with and without a latency reversal agent-AZD5582, an activator of the non-canonical NFκB pathway-to examine a combination of mechanisms controlling HIV-1 latency. A component of the Nucleosome Acetyltransferase of H4 histone acetylation (NuA4 HAT) complex, ING3, acts in concert with AZD5582 to activate proviruses in J-Lat cell lines and in a primary CD4+ T cell model of HIV-1 latency. We found that the knockout of ING3 reduces acetylation of the H4 histone tail and BRD4 occupancy on the HIV-1 LTR. However, the combination of ING3 knockout accompanied with the activation of the non-canonical NFκB pathway via AZD5582 resulted in a dramatic increase in initiation and elongation of RNA Polymerase II on the HIV-1 provirus in a manner that is nearly unique among all cellular promoters., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsieh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint blockade is central to Immuno-Oncology based therapies, and alternatives to antibody blockers of this interaction are an active area of research due to antibody related toxicities. Recently, small molecule compounds that induce PD-L1 dimerization and occlusion of PD-1 binding site have been identified and developed for clinical trials. This mechanism invokes an oligomeric state of PD-L1 not observed in cells previously, as PD-L1 is generally believed to function as a monomer. Therefore, understanding the cellular lifecycle of the induced PD-L1 dimer is of keen interest. Our report describes a moderate but consistent increase in the PD-L1 rate of degradation observed upon protein dimerization as compared to the monomer counterpart. This subtle change, while not resolved by measuring total PD-L1 cellular levels by western blotting, triggered investigations of the overall protein distribution across various cellular compartments. We show that PD-L1 dimerization does not lead to rapid internalization of neither transfected nor endogenously expressed protein forms. Instead, evidence is presented that dimerization results in retention of PD-L1 intracellularly, which concomitantly correlates with its reduction on the cell surface. Therefore, the obtained data for the first time points to the ability of small molecules to induce dimerization of the newly synthesized PD-L1 in addition to the protein already present on the plasma membrane. Overall, this work serves to improve our understanding of this important target on a molecular level in order to guide advances in drug development., (© 2022. The Author(s).)

Competing Interests: Competing interests: None declared.

Doctors and patients rely on verbal and nonverbal resources to co-construct clinical empathy. In language-discordant consultations, interpreters' communicative actions might compromise this process. We aim to explore doctors, patients, and professional interpreters' perspectives on their own and others' actions during their empathic interaction in interpreter-mediated consultations (IMCs). We analyzed 20 video stimulated recall interviews with doctors, patients, and interpreters using qualitative content analysis. Doctors and patients found ways to connect with each other on the level of empathic communication (EC) that is not limited by interpreters' alterations or disengaged demeanor. Some aspects of doctors and interpreters' professional practices might jeopardize the co-construction of EC in IMCs. The co-construction of EC in IMCs is not only subject to participants' communicative (inter)actions, but also to organizational and subjective factors. These results provide evidence of the transactional process between the behavioral, cognitive, and affective components of clinical empathy in the context of IMCs.

Background: Older (older than 50 years) persons living with HIV (PWH) are at elevated risk for falls. We explored how well our algorithm for predicting falls in a general population of middle-aged Veterans (age 45-65 years) worked among older PWH who use antiretroviral therapy (ART) and whether model fit improved with inclusion of specific ART classes., Methods: This analysis included 304,951 six-month person-intervals over a 15-year period (2001-2015) contributed by 26,373 older PWH from the Veterans Aging Cohort Study who were taking ART. Serious falls (those falls warranting a visit to a health care provider) were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Potential predictors included a fall within the past 12 months, demographics, body mass index, Veterans Aging Cohort Study Index 2.0 score, substance use, and measures of multimorbidity and polypharmacy. We assessed discrimination and calibration from application of the original coefficients (model derived from middle-aged Veterans) to older PWH and then reassessed by refitting the model using multivariable logistic regression with generalized estimating equations. We also explored whether model performance improved with indicators of ART classes., Results: With application of the original coefficients, discrimination was good (C-statistic 0.725; 95% CI: 0.719 to 0.730) but calibration was poor. After refitting the model, both discrimination (C-statistic 0.732; 95% CI: 0.727 to 0.734) and calibration were good. Including ART classes did not improve model performance., Conclusions: After refitting their coefficients, the same variables predicted risk of serious falls among older PWH nearly and they had among middle-aged Veterans., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Elimination of hepatitis C virus (HCV), a leading cause of liver disease in the USA and globally, has been made possible with the advent of highly efficacious direct acting antivirals (DAAs). DAA regimens offer cure of HCV with 8-12 weeks of a well-tolerated once daily therapy. With increasingly straightforward diagnostic and treatment algorithms, HCV infection can be managed not only by specialists, but also by primary care providers. Engaging primary care providers greatly increases capacity to diagnose and treat chronic HCV and ultimately make HCV elimination a reality. However, barriers remain at each step in the HCV cascade of care from screening to evaluation and treatment. Since primary care is at the forefront of patient contact, it represents the ideal place to concentrate efforts to identify barriers and implement solutions to achieve universal HCV screening and increase curative treatment., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs)., Methods: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression., Results: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81)., Conclusion: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs., Competing Interests: Competing interests: MP reports grants from AbbVie—SELECT-GCA Participating Center and AstraZeneca—MANDARA Participating Center; and consulting fees from Novartis, outside the submitted work. ES is a board member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. SES reports research funding related to clinical trials from AstraZeneca (MANDARA) and is supported by the Vasculitis Clinical Research Consortium and Vasculitis Foundation, outside the submitted work. CH is a stockholder for Aurinia Pharmaceuticals; an Advisory Board member for Aurinia Pharmaceuticals, AstraZeneca Pharmaceuticals and UCB Pharmaceuticals; and reports consulting fees from AstraZeneca, UCB, Antidote and Aurinia Pharmaceuticals, outside the submitted work. MJL reports grants from American College of Rheumatology, during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gilead, Johnson & Johnson, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi and Union Chimique Belge, outside the submitted work. SB reports non-branded consulting fees from AbbVie, Amgen, Horizon Pharma, Novartis and Pfizer outside the submitted work, and is a Pfizer employee as of September 2021. RG reports speaker honoraria from AbbVie New Zealand, Cornerstones and Janssen New Zealand; speaker honoraria and non-financial support Pfizer Australia; non-financial support from Janssen Australia and personal fees from Novartis (all <$A10 000) outside the submitted work. PMM reports consulting fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and Union Chimique Belge; and grants and consulting fees from Orphazyme, outside the submitted work. PCR reports personal fees from AbbVie, Gilead, Eli Lilly and Roche; grants and personal fees from Novartis, Union Chimique Belge, Janssen and Pfizer and non-financial support from Bristol Myers Squibb, outside the submitted work. ZSW reports grants from NIH, Bristol Myers Squibb and Principia/Sanofi; and personal fees from Viela Bio and MedPace, outside the submitted work. JY reports grants from NIH/NIAMS K24 during the conduct of the study and outside the submitted work, reports research grants from Gilead, BMS Foundation and AstraZeneca; consulting fees from Pfizer, AstraZeneca and Aurinia. MG-M reports consulting fees for BMS, BI, JNJ and Aurinia (all <$A10 000), outside the submitted work. RH reports grants from AbbVie, Amgen, Boehringer Ingleheim, Johnson & Johnson, Eli Lilly, Novartis, Pfizer and Union Chimique Belge, all paid to Spondylitis Association of America, and consultant fees from GlaxoSmithKline and Novartis, outside the submitted work. RH also owns stocks (<20 shares and representing <4% of personal investments) in AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Merck, Novartis, Pfizer, Teva and Union Chimique Belge. DA-R is a scientific advisor for and reports personal fees from GlaxoSmithKilne Mexico unrelated to this work. RC reports speaker fees from Janssen, Roche, Sanofi and AbbVie, outside the submitted work. AD-G reports grants from the Centers for Disease Control and Prevention, Rheumatology Research Foundation and Mayo Clinic, outside the submitted work. JAS has received consultant fees from Schipher, Crealta/Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS has received institutional research support from Zimmer Biomet Holdings. JAS received food and beverage payments from Intuitive Surgical/Philips Electronics North America. JAS owns stock options in TPT Global Tech, Vaxart Pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals Holding and Charlotte’s Web Holdings. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker’s bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organisation that develops outcome measures in rheumatology and receives arms-length funding from eight companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Board (FAB). JAS is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. MFU-G reports research grants from Pfizer and Janssen, unrelated to this work. JSH reports grants from and Rheumatology Research Alliance; consulting fees from Novartis, Pfizer and Biogen; and is a member of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). JFS received research grant funding from the National Institutes of Health unrelated to this work (NIAMS R01 AR077103 and NIAID R01 AI154533). JSp is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR077607, P30 AR070253 and P30 AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, the Llura Gund Award for Rheumatoid Arthritis Research and Care and Bristol Myers Squibb; and personal fees for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum and Pfizer, unrelated to this work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The TILES-2019 data set consists of behavioral and physiological data gathered from 57 medical residents (i.e., trainees) working in an intensive care unit (ICU) in the United States. The data set allows for the exploration of longitudinal changes in well-being, teamwork, and job performance in a demanding environment, as residents worked in the ICU for three weeks. Residents wore a Fitbit, a Bluetooth-based proximity sensor, and an audio-feature recorder. They completed daily surveys and interviews at the beginning and end of their rotation. In addition, we collected data from environmental sensors (i.e., Internet-of-Things Bluetooth data hubs) and obtained hospital records (e.g., patient census) and residents' job evaluations. This data set may be may be of interest to researchers interested in workplace stress, group dynamics, social support, the physical and psychological effects of witnessing patient deaths, predicting survey data from sensors, and privacy-aware and privacy-preserving machine learning. Notably, a small subset of the data was collected during the first wave of the COVID-19 pandemic., (© 2022. The Author(s).)

Background: α-Synuclein (αSyn) is believed to play a central role in Parkinson's disease (PD) neuropathology and is considered a target for disease modification. UB-312 is a synthetic αSyn peptide conjugated to a T helper peptide and is expected to induce antibodies specifically against oligomeric and fibrillar αSyn, making UB-312 a potential immunotherapeutic for synucleopathies., Objective: To investigate the safety, tolerability, and immunogenicity of UB-312 vaccination in healthy participants and to determine a safe and immunologically optimal dose for the first-in-patient study., Methods: Fifty eligible healthy participants were enrolled in a 44-week, randomized, placebo-controlled, double-blind study. Participants in seven cohorts were randomized to three intramuscular UB-312 or placebo injections at weeks 1, 5, and 13 (doses ranging between 40 and 2000 μg). Safety and tolerability were assessed by adverse events, clinical laboratory, vital signs, electrocardiograms, and neurological and physical examinations. Immunogenicity was assessed by measuring serum and cerebrospinal fluid (CSF) anti-αSyn antibody concentrations., Results: Twenty-three participants received all three vaccinations of UB-312. Most adverse events were mild, transient, and self-resolving. Common treatment-emergent adverse events included headache, nasopharyngitis, vaccination-site pain, lumbar puncture-site pain, and fatigue. UB-312 induced dose- and time-dependent antibody production. Antibodies were detectable in serum and CSF of all participants receiving the 300/300/300 μg UB-312 dose regimen. The average CSF/serum ratio was 0.2%., Conclusions: UB-312 was generally safe, well tolerated, and induced anti-αSyn antibodies in serum and CSF of healthy participants. The 100 and 300 μg doses are selected for further evaluation in participants with PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Competing Interests: Competing interests: None declared.

Background: Studies have shown that women aging with HIV have significantly lower health-related quality of life (HRQoL) compared to women without HIV. However, no studies have examined this issue in Latin America and the Caribbean. We aimed to explore HRQoL measured by the 36-Item Short Form Health Survey (SF-36) among women aging with and without HIV in Peru., Materials and Methods: We conducted a cross-sectional study at a large HIV-clinic in Peru. Outcomes of the SF-36 were evaluated, exploring the relationship between physical activity (International Physical Activity Questionnaire), sociodemographic factors (ethnicity, alcohol/tobacco use, age, BMI) and clinical data (AIDS progression, treatment duration, CD4+ cell count and viral load, years since HIV diagnosis) with HRQoL using regression analysis. Statistical significance was set with a two-tailed p-value <0.05., Results: We enrolled 427 women (175 HIV-infected) with mean age of 54±8 years. From the SF-36 individual domains: physical functioning, role limitations due to physical and emotional health, and emotional wellbeing were significantly lower for HIV-infected women. Summary component scores were lower for the HIV-subset for both physical (45.8 vs 47.3) and mental (45.1 vs 45.8) components, although they did not achieve statistical significance. Regression analysis of the HIV-infected women revealed that the physical component score was significantly associated with physical activity, ethnicity, and chronic comorbidities while the mental component was significantly associated with physical activity, employment, and CD4+ cell count., Conclusion: In our study, HIV-infected women scored lower in both physical and mental component scores. Important determinants for each component included CD4+ cell count as an assessment of HIV severity for the mental component, and ethnicity, reflecting socio-cultural factors, for the physical component. These results reveal the importance of a holistic approach to addressing HRQoL in this population. Better understanding of these factors will help shape future policies and interventions to improve HRQoL of women aging with HIV., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim was to assess rheumatology clinicians' perceptions of telemedicine and their experiences before and during the coronavirus disease 2019 (COVID-19) pandemic., Methods: We conducted a cross-sectional online survey and collected responses from rheumatology clinicians worldwide, between November 2020 and February 2021, regarding use and perceptions of telemedicine in rheumatology. We summarized data with descriptive statistics and qualitative analysis for free-text responses., Results: The survey was completed by 349 rheumatology clinicians from 49 countries; 59% were female and about two-thirds were in the 30-50 years age group. Academic affiliations were held by 55% of participants, and 44% were from North America. Before the pandemic, 24% of participants had experience with telemedicine, whereas about three-quarters used telemedicine for the first time during the pandemic. Overall, 56% thought they provided less adequate care with telemedicine. More than half of clinicians felt that telemedicine was adequate for evaluating crystalline arthritis, inflammatory arthritis and lupus flares. Telemedicine was felt to be inadequate for flares of myositis, vasculitis and scleroderma. Technical problems were reported in 29% of telemedicine encounters and were most commonly related to patient-encountered difficulties., Conclusion: Most rheumatology clinicians used telemedicine for the first time during the pandemic. The quality of care provided was thought to be inferior to that provided in person for specific clinical situations. Additional efforts are needed to address barriers to effective telemedicine, such as patient-related technology issues, challenges with building rapport and performing a physical examination, and to define the appropriate scope of clinical scenarios conducive to telemedicine., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients., Methods: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models., Results: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD., Conclusion: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

People ageing with HIV face crucial challenges that can compromise their long-term health, one of which is stigma. HIV-related stigma can interact with other coexistent inequities to create a unique oppression system that results in traumatic experiences. This intersectionality of stigmas represents a new inequality that is greater than the sum of the original component inequalities. In this Series paper we review the literature regarding the intersectionality of HIV-related and ageing-related stigma and health-related quality of life among people ageing with HIV in China, Europe, and Latin America-three regions that represent distinct epidemiological and cultural trends in terms of HIV and ageing. Substantial gaps in the literature were identified, in particular a scarcity of data from Latin America. We also found inconsistencies between countries in terms of definitions and reporting practices related to people ageing with HIV. Research that fully considers the intersectional stigmas faced by this vulnerable population will contribute to advancing the United Nations 2030 Agenda for Sustainable Development., Competing Interests: Declaration of interests MJF-R is the executive director of the Spanish Interdisciplinary AIDS Society (SEISIDA). SEISIDA has received grants from Gilead Sciences, Janssen, Merck Sharp & Dohme (MSD), and ViiV Healthcare, outside of the submitted work. MJF-R has provided consultancy services to Gilead Sciences, Janssen, MSD, ViiV Healthcare, and Theratechnologies, and has received payments for lectures or educational presentations from Gilead Sciences, Janssen, MSD, and ViiV Healthcare, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To systematically review and evaluate the prevalence, potential predictors, and prognostic benefits of remission achievement in patients with systemic lupus erythematosus (SLE)., Methods: Studies reporting on the prevalence, predictors, and prognostic benefits of remission in adult patients with SLE were searched and selected from PubMed and Embase databases. Studies were reviewed for relevance and quality. Two reviewers independently assessed the studies and extracted data., Results: Data from 41 studies including 17,270 patients were included and analyzed. Although no consensus has been achieved on the definition of remission, clinical disease activity, serologic activity, duration, and treatment are agreed to be critical components of defining remission status. In most studies published in the recent 5 years, 42.4-88% of patients achieved and maintained the remission status for 1 year, and 21.1-70% did so for at least 5 years. Factors associated with remission included older age at diagnosis, lower baseline disease activity, and absence of major organ involvement, while positive serologic results were shown to be negatively associated with remission. Remission (especially prolonged remission) when achieved, demonstrated an association with lower accrual of damage and better quality of life among patients with SLE., Conclusion: Remission is an achievable and desirable target for SLE patients and proven to be associated with prognostic benefits. Further development and assessment of a clear remission definition, a risk stratification model, as well as a full algorithm with frequency of monitoring time points for treatment adjustment and drug withdrawal are required., (© 2020, American College of Rheumatology.)

Context.—: Competency-based medical education relies on frequent formative in-service assessments to ascertain trainee progression. Currently at our institution, trainees receive a summative end-of-rotation In-Training Evaluation Report based on feedback collected from staff pathologists. There is no method of simulating report sign-out., Objective.—: To develop a formative in-service assessment tool that is able to simulate report sign-out and provide case-by-case feedback to trainees. Further, to compare time- versus competency-based assessment models., Design.—: Twenty-one pathology trainees were assessed for 20 months. Hot Seat Diagnosis by trainees and trainee assessment by pathologists were recorded in the laboratory information system. In the first iteration, trainees were assessed by using a time-based assessment scale on their ability to diagnose, report, use ancillary tests, comment on clinical implications, and provide intraoperative consultation and/or gross cases. The second iteration used a competency-based assessment scale. Trainees and pathologists completed surveys on the effectiveness of the In-Training Evaluation Report versus the Hot Seat Diagnosis tool., Results.—: Scores from both iterations correlated significantly with other assessment tools including the Resident In-Service Examination (r = 0.93, P = .04 and r = 0.87, P = .03). The competency-based model was better able to demonstrate improvement over time and stratify junior versus senior trainees than the time-based model. Trainees and pathologists rated Hot Seat Diagnosis as significantly more objective, detailed, and timely than the In-Training Evaluation Report, and effective at simulating report sign-out., Conclusions.—: Hot Seat Diagnosis is an effective tool for the formative in-service assessment of pathology trainees and simulation of report sign-out, with the competency-based model outperforming the time-based model.