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Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N -oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. Methods: This is an observational case:control study. Adults with SSc ( n = 200) and non-SSc controls ( n = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Results: Median TMAO concentration was higher ( p = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Conclusions: Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted.

Objective: In individuals without radiographic knee osteoarthritis (OA), we investigated whether magnetic resonance imaging (MRI)-defined knee OA at baseline was associated with incident radiographic and symptomatic disease during up to 11 years of follow-up., Methods: Osteoarthritis Initiative participants without tibiofemoral radiographic knee OA at baseline were assessed for MRI-based tibiofemoral cartilage damage, osteophyte presence, bone marrow lesions, and meniscal damage/extrusion. We defined MRI knee OA using alternative, reported definitions (Def A and Def B). Kellgren-Lawrence (KL) grade, joint space narrowing (JSN), and frequent knee symptoms (Sx) were assessed at baseline, 1-, 2-, 3-, 4-, 6-, 8-, and 10/11-year follow-up visits. Incident tibiofemoral radiographic knee OA (outcome) was defined as (1) KL ≥2, (2) KL ≥2 and JSN, or (3) KL ≥2 and Sx. Adjusted Cox proportional hazards regression models examined associations of baseline MRI-defined knee OA (Def A and Def B) with incident outcomes during up to 11 years of follow-up., Results: Among 1,621 participants (mean age ± SD 58.8 ± 9.0 years, mean body mass index ± SD 27.2 ± 4.5 kg/m 2 , 59.5% women), 17% had MRI-defined knee OA by Def A and 24% by Def B. Baseline MRI-defined knee OA was associated with incident KL ≥2 (odds ratio 2.94 [95% confidence interval (95% CI) 2.34-3.68] for Def A and 2.44 [95% CI 1.97-3.03] for Def B). However, a substantial proportion of individuals with baseline MRI-defined knee OA did not develop incident KL ≥2 during follow-up (59% for Def A and 64% for Def B). Findings were similar for the other two outcomes., Conclusion: Current MRI definitions of knee OA do not adequately identify knees that will develop radiographic and symptomatic disease., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: Inequities in COVID-19 infection and vaccine uptake among historically marginalised racial and ethnic groups in the USA persist. Individuals with rheumatic conditions, especially those who are immunocompromised, are especially vulnerable to severe infection, with significant racialised inequities in infection outcomes and in vaccine uptake. Structural racism, historical injustices and misinformation engender racial and ethnic inequities in vaccine uptake. The Popular Opinion Lleader (POL) model, a community-based intervention that trains trusted community leaders to disseminate health information to their social network members (eg, friends, family and neighbours), has been shown to reduce stigma and improve care-seeking behaviours., Methods and Analysis: This is a community-based cluster randomised controlled trial led by a team of community and academic partners to compare the efficacy of training POLs with rheumatic or musculoskeletal conditions using a curriculum embedded with a racial justice vs a biomedical framework to increase COVID-19 vaccine uptake and reduce vaccine hesitancy. This trial began recruitment in February 2024 in Boston, Massachusetts and Chicago, Illinois, USA. Eligible POLs are English-speaking adults who identify as Black and/or of African descent, have a diagnosis of a rheumatic or musculoskeletal condition and have received >=1 COVID-19 vaccine after 31 August 2022. POLs will be randomised to a 6-module virtual educational training; the COVID-19 and vaccine-related content will be the same for both groups however the framing for arm 1 will be with a racial justice lens and for arm 2, a biomedical preventative care-focused lens. Following the training, POLs will disseminate the information they learned to 12-16 social network members who have not received the most recent COVID-19 vaccine, over 4 weeks. The trial's primary outcome is social network member COVID-19 vaccine uptake, which will be compared between intervention arms., Ethics and Dissemination: This trial has ethical approval in the USA. This has been approved by the Mass General Brigham Institutional Review Board (IRB, 2023P000686), the Northwestern University IRB (STU00219053), the Boston University/Boston Medical Center IRB (H-43857) and the Boston Children's Hospital IRB (P00045404). Results will be published in a publicly accessible peer-reviewed journal., Trial Registration Number: NCT05822219., Competing Interests: Competing interests: RG-R receives research support from her institution (Northwestern), from the NIH, the Lupus Foundation of America, the American College of Rheumatology, The Medical University of South Carolina, the University of Alabama and the Lupus Research Alliance (LuCIN). She receives consulting fees from the State University of New York, Syracuse, Merck, Biogen, Exagen Diagnostics, Duke University, Ampel Solutions, Clarivate, Bristol Myers Squibb and Cabaletta. She received honoraria from AstraZeneca and Georgetown University, and she previously served as the Chair of the COIN Committee for the American College of Rheumatology. CF receives research support to her institution from the NIH/NIAMS, the Arthritis Foundation and the BMS Foundation. She has served as a consultant on grants to the American College of Rheumatology, Lupus Foundation of America and the University of Alabama and has consulted for Bain Capital, LP, Harvard Pilgrim and OM1. CF received honoraria for presentations at Northwestern University and the University of Alabama, Birmingham. She is the Lupus Science & Medicine Associate Editor and is a former Associate Editor for ACR Open Rheumatology. CF serves on the AC&R Editorial Board, the AF DEI Task Force, the ACR DEI Committee, and LFA Medical and Scientific Advisory Board. MC receives research support from the NIH, Childhood Arthritis and Rheumatology Research Alliance, Honoria at the Roxbury YMCA and meeting/travel support from the Lupus Research Alliance. JW receives support from Bristol Myers Squibb Foundation, and Lupus Research Alliance. She receives consulting fees from CVS Pharmacy, honoraria from the Lupus Foundation of America and meeting/travel support from RILITE Foundation. JW serves on the Lupus Foundation of America–Medical Scientific Advisory Council, NIH-NIAMS P30 VERITY Research Community External Advisory Board, Project CHANGE by Lupus Therapeutics steering committee, American College of Rheumatology Systemic Lupus Erythematosus and Lupus Nephritis Guideline Development Group and American College of Rheumatology Research and Publications Subcommittee (October 2020-October 2023). AD, BO, DE, EL, GS, LNM, MSon, MC-B, MJ-J, MY, NP, TR and HM receive support from the NIH (NIAMS R01 AR 080089). All other authors have no relevant financial disclosures or conflict of interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To characterize sleep disturbance in patients with established rheumatoid arthritis (RA) and explore the relationship between sleep and mechanisms of central nervous system pain regulation., Methods: Forty-eight RA participants completed wrist-worn actigraphy monitoring and daily sleep diaries for 14 days to assess sleep-wake parameters. Participants underwent quantitative sensory testing to assess pressure pain thresholds, temporal summation, and conditioned pain modulation. Data were analyzed using descriptive statistics, Spearman's correlation, and multivariable median regression analyses., Results: Median actigraphy and sleep diary derived sleep duration was 7.6 h (interquartile range (IQR) 7.0, 8.2) and 7.1 h (IQR 6.7, 7.6), respectively. Actigraphy based sleep fragmentation (rho = 0.34), wake after sleep onset (rho = 0.36), and sleep efficiency (rho = -0.32) were each related to higher temporal summation values in unadjusted analyses, but these relationships did not persist after controlling for age, body mass index, disease duration, and swollen joint count. No significant relationships were observed between sleep with pressure pain thresholds and conditioned pain modulation., Conclusion: Actigraphy and sleep diary monitoring are well tolerated in established RA patients. Future investigations should include both subjective and objective assessments, as they may provide information relating to different components and mechanisms., (© 2024. The Author(s).)

Background: Catheter ablation for atrial fibrillation (AFCA) has been shown to reduce AF burden and improve quality of life. Earlier studies demonstrated that women are less likely to undergo AFCA despite having more AF symptoms. We investigated whether an association exists between referral patterns and this sex disparity., Methods: A retrospective cohort study was conducted of outpatients with newly diagnosed AF at a single tertiary referral center. Logistic regression models adjusted for socioeconomic and clinical factors were constructed to determine associations between sex and binary dependent variables including referrals to and visits with general cardiology and electrophysiology (EP) and AFCA utilization., Results: Of 6850 patients analyzed, 2693 were women, and 4157 were men. No significant differences were found in odds of referral to (aOR, 1.13 [0.92-1.40], P = 0.25) or visits with (aOR, 1.05 [0.86-1.29], P = 0.62) general cardiologists between women and men. Women were found to be less likely to visit with EP than men (aOR, 0.88 [0.79-0.99], P = 0.03). In analyses of referral patterns after release of the 2014 AHA/ACC/HRS guidelines, women were found to be referred to (aOR, 0.78 [0.63-0.95], P = 0.01) and visit with (aOR, 0.86 [0.75-0.99], P = 0.03) EP less frequently than men. Finally, no significant difference was found in likelihood to undergo AFCA between women and men (aOR, 1.05 [0.83-1.33], P = 0.67)., Conclusions: This study uncovered significant differences in rates of referral to and visits with EP between women and men. Encouraging equitable referral to specialists and access to AFCA is essential in ensuring appropriate care for all patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Becoming a parent is a transformative experience requiring multiple transitions, including the need to navigate several components of health care, manage any mental health issues, and develop and sustain an approach to infant feeding. Baby2Home (B2H) is a digital intervention built on the collaborative care model (CCM) designed to support families during these transitions to parenthood., Objectives: We aim to investigate the effects of B2H on preventive healthcare utilization for the family unit and patient-reported outcomes (PROs) trajectories with a focus on mental health. We also aim to evaluate heterogeneity in treatment effects across social determinants of health including self-reported race and ethnicity and household income. We hypothesize that B2H will lead to optimized healthcare utilization, improved PROs trajectories, and reduced racial, ethnic, and income-based disparities in these outcomes as compared to usual care., Methods: B2H is a multi-center, pragmatic, individual-level randomized controlled trial. We will enroll 640 families who will be randomized to: [1] B2H + usual care, or [2] usual care alone. Preventive healthcare utilization is self-reported and confirmed from medical records and includes attendance at the postpartum visit, contraception use, depression screening, vaccine uptake, well-baby visit attendance, and breastfeeding at 6 months. PROs trajectories will be analyzed after collection at 1 month, 2 months, 4 months, 6 months and 12 months. PROs include assessments of stress, depression, anxiety, self-efficacy and relationship health., Implications: If B2H proves effective, it would provide a scalable digital intervention to improve care for families throughout the transition to new parenthood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown., Objective: The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS., Methods: MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels., Results: A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP level was higher in patients undergoing extensive surgery., Conclusion: ESS decreased levels of IL-13 and periostin in the middle meatus. T2 inflammation after ESS was correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Clinical chatbots are increasingly used to help integrate genetic testing into clinical contexts, but no chatbot exists for Apolipoprotein L1 (APOL1) genetic testing of living kidney donor (LKD) candidates of African ancestry. Our study aimed to culturally adapt and assess perceptions of the Gia® chatbot to help integrate APOL1 testing into LKD evaluation. Ten focus groups and post-focus group surveys were conducted with 54 LKDs, community members, and kidney transplant recipients of African ancestry. Data were analyzed through thematic analysis and descriptive statistics. Key themes about making Gia culturally targeted included ensuring: (1) transparency by providing Black LKDs' testimonials, explaining patient privacy and confidentiality protections, and explaining how genetic testing can help LKD evaluation; (2) content is informative by educating Black LKDs about APOL1 testing instead of aiming to convince them to undergo testing, presenting statistics, and describing how genetic discrimination is legally prevented; and (3) content avoids stigma about living donation in the Black community. Most agreed Gia was neutral and unbiased (82%), trustworthy (82%), and words, phrases, and expressions were familiar to the intended audience (85%). Our culturally adapted APOL1 Gia chatbot was well regarded. Future research should assess how this chatbot could supplement provider discussion prior to genetic testing to scale APOL1 counseling and testing for LKD candidate clinical evaluation., (© 2024. The Author(s).)

Objective: To identify modifiable physical and behavioural factors associated with widespread pain (WSP) in older adults with radiographic evidence of knee osteoarthritis (OA)., Methods: Cross-sectional initial visit data of participants with radiographic knee OA (Kellgren-Lawrence grade of ≥2) from the Osteoarthritis Initiative Study were analysed. WSP was defined as pain on both sides of the body, above and below the waist, and in the axial skeleton. Time (hrs/d) spent participating in sitting and moderate-strenuous physical activities were calculated from the Physical Activity Scale for the Elderly questionnaire. Physical function was quantified using gait speed and the chair stand test. Restless sleep was assessed using an item on the CES-D Scale. Logistic regression models were constructed to examine the strength of the associations between primary exposures and WSP in unadjusted and adjusted analyses., Results: Among the 2637 participants (mean age 62.6 years, 58.6% female), 16.8% met the criteria for WSP. All primary measures of interest were related to WSP in unadjusted analyses. In adjusted multivariable analysis, slow gait speed (adjusted odds ratio [aOR] 1.43; 95% CI 1.01, 2.02), lower chair stand rate (aOR 0.98; 95% CI 0.97-0.99), and restless sleep (aOR 1.61; 95% CI 1.25-2.08) maintained significant associations with WSP., Conclusion: Poor sleep behaviours and low physical function capacity are associated with WSP in adults with radiographic knee OA. These findings highlight the importance of assessing sleep, physical function, and pain distribution in this population. Interventions to improve physical function and sleep behaviours should be investigated as potential strategies to mitigate WSP., (© 2023 John Wiley & Sons Ltd.)

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/m 2 ; 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., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA., Methods: This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein., Results: Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed., Conclusion: Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: While natural cycle frozen embryo transfer (NC-FET) is becoming increasingly common, significant practice variation exists in the use of ovulation induction medications, administration of ovulation trigger, and timing of embryo transfer without consensus as to the optimal protocol., Aims: The objective of this study is to evaluate the association of key aspects of the NC-FET protocol with implantation, pregnancy and live birth., Settings and Design: This was a retrospective cohort study of blastocyst stage NC-FET cycles from October 2019 to July 2021 at a single academic fertility centre., Materials and Methods: Protocols varied between cycles across three key parameters which were evaluated as primary predictors of cycle outcomes: (1) use of letrozole for mild ovarian stimulation/ovulation induction, (2) administration of exogenous ovulation trigger versus spontaneous luteinising hormone surge and (3) transfer timing based on ovulation trigger versus sequential progesterone monitoring. Primary outcomes included implantation rate, clinical pregnancy and ongoing pregnancy., Statistical Analysis Used: Generalised estimating equations were fitted to obtain adjusted odds ratios or rate ratios as appropriate with 95% confidence intervals for each outcome across the three primary predictors., Results: A total of 183 cycles from 170 unique patients were eligible for inclusion. The average implantation rate was 0.58, resulting in an overall clinical pregnancy and ongoing pregnancy rate of 59.0% and 51.4%, respectively. After adjusting for age at embryo freeze and history of a failed embryo transfer, there were no significant associations between any predictor and implantation rate, clinical pregnancy, ongoing pregnancy, or live birth., Conclusion: In NC-FET, a variety of preparation and timing protocols may lead to comparable cycle outcomes, potentially allowing for flexibility on the basis of patient and physician preference. These findings warrant validation in a larger, randomised trial., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

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., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Objective: Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment., Methods: Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment., Results: This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1])., Conclusion: These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy., (Copyright © 2023 by the Journal of Rheumatology.)

Introduction: While living donor (LD) kidney transplantation is the optimal treatment for patients with kidney failure, LDs assume a higher risk of future kidney failure themselves. LDs of African ancestry have an even greater risk of kidney failure post-donation than White LDs. Because evidence suggests that Apolipoprotein L1 ( APOL1 ) risk variants contribute to this greater risk, transplant nephrologists are increasingly using APOL1 genetic testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counselling with LD candidates about APOL1 due to a lack of knowledge and skill in counselling. Without proper counselling, APOL1 testing will magnify LD candidates' decisional conflict about donating, jeopardising their informed consent. Given cultural concerns about genetic testing among people of African ancestry, protecting LD candidates' safety is essential to improve informed decisions about donating. Clinical 'chatbots', mobile apps that provide genetic information to patients, can improve informed treatment decisions. No chatbot on APOL1 is available and no nephrologist training programmes are available to provide culturally competent counselling to LDs about APOL1 . Given the shortage of genetic counsellors, increasing nephrologists' genetic literacy is critical to integrating genetic testing into practice., Methods and Analysis: Using a non-randomised, pre-post trial design in two transplant centres (Chicago, IL, and Washington, DC), we will evaluate the effectiveness of culturally competent APOL1 testing, chatbot and counselling on LD candidates' decisional conflict about donating, preparedness for decision-making, willingness to donate and satisfaction with informed consent and longitudinally evaluate the implementation of this intervention into clinical practice using the R each, E ffectiveness, A doption, I mplementation and M aintenance framework., Ethics and Dissemination: This study will create a model for APOL1 testing of LDs of African ancestry, which can be implemented nationally via implementation science approaches. APOL1 will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve informed consent. This study involves human participants and was approved by Northwestern University IRB (STU00214038). Participants gave informed consent to participate in the study before taking part., Trial Registration: ClinicalTrials.gov Identifier: NCT04910867. Registered 8 May 2021, https://register., Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S000AWZ6&selectaction=Edit&uid=U0001PPF&ts=7&cx=-8jv7m2 ClinicalTrials.gov Identifier: NCT04999436. Registered 5 November 2021, https://register., Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S000AYWW&selectaction=Edit&uid=U0001PPF&ts=11&cx=9tny7v., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD)., Methods: One hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables., Results: In multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04, P = 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08, P = 0.001), whereas the SSS was not (B = -0.03, P = 0.43)., Conclusion: Higher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ's prediction of disease activity was the spatial extent of pain, as measured by the WPI., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Patients with diffuse cutaneous systemic sclerosis (dcSSc) display a complex clinical phenotype. Transcriptional profiling of whole blood or tissue from patients are affected by changes in cellular composition that drive gene expression and an inability to detect minority cell populations. We undertook this study to focus on the 2 main subtypes of circulating monocytes, classical monocytes (CMs) and nonclassical monocytes (NCMs) as a biomarker of SSc disease severity., Methods: SSc patients were recruited from the Prospective Registry for Early Systemic Sclerosis. Clinical data were collected, as well as peripheral blood for isolation of CMs and NCMs. Age-, sex-, and race-matched healthy volunteers were recruited as controls. Bulk macrophages were isolated from the skin in a separate cohort. All samples were assayed by RNA sequencing (RNA-seq)., Results: We used an unbiased approach to cluster patients into 3 groups (groups A-C) based on the transcriptional signatures of CMs relative to controls. Each group maintained their characteristic transcriptional signature in NCMs. Genes up-regulated in group C demonstrated the highest expression compared to the other groups in SSc skin macrophages, relative to controls. Patients from groups B and C exhibited worse lung function than group A, although there was no difference in SSc skin disease at baseline, relative to controls. We validated our approach by applying our group classifications to published bulk monocyte RNA-seq data from SSc patients, and we found that patients without skin disease were most likely to be classified as group A., Conclusion: We are the first to show that transcriptional signatures of CMs and NCMs can be used to unbiasedly stratify SSc patients and correlate with disease activity outcome measures., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain., Methods: We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors., Results: Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect., Conclusion: Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background Guidelines recommend catheter ablation of atrial fibrillation (AFCA) as an option for rhythm control. Studies have shown that Black patients are less likely to undergo AFCA compared with White patients. We investigated whether differences in referral patterns play a role in this observed disparity. Methods and Results Using an integrated repository from the electronic medical record at Northwestern Medicine, we conducted a retrospective cohort study of outpatients with newly diagnosed atrial fibrillation. Baseline characteristics by race and ethnicity were compared. Logistic regression models adjusted for socioeconomic and health factors were constructed to determine the association between race and ethnicity and binary dependent variables including referrals and visits to general cardiology and cardiac electrophysiology (EP) and AFCA. Of 5445 patients analyzed, 4652 were non-Hispanic White (NHW) and 793 were non-Hispanic Black (NHB). In adjusted models, NHB patients initially diagnosed with atrial fibrillation in internal medicine and primary care had a significantly greater odds of referral to general cardiology; among all patients in the cohort, there was no significant difference in the odds of referral to EP between NHB and NHW patients; and there were no differences in the odds of completing a visit in general cardiology or EP. Among patients completing an EP visit, NHB patients were less likely to undergo AFCA (odds ratio, 0.63 [95% CI, 0.40-0.98], P =0.040). Conclusions Similar referral rates to general cardiology and EP were observed between NHB and NHW patients. Despite this, NHB patients were less likely to undergo AFCA.

Background: A growing body of literature describes abdominal aesthetic goals to tailor surgical and nonsurgical treatment options to meet patient goals. The authors aimed to integrate layperson perceptions into the design of a novel professional aesthetic scale for the abdomen., Methods: An iterative process of expert consensus was used to choose five domains: abdominal muscle lines, abdominal shape, scar, skin, and umbilicus. A survey was developed to measure global and domain-specific aesthetic preferences on five abdomens. This was distributed through Amazon Mechanical Turk to 340 respondents. Principal component analysis was used to integrate survey data into weights for each of the scale's subquestions. Attending plastic surgeons then rated abdomens using the final scale, and reliability and validity were calculated., Results: The final scale included 11 subquestions-hourglass shape, bulges, hernia, infraumbilical skin, supraumbilical skin, umbilicus shape, umbilicus medialization position, umbilicus height position, semilunar lines, central midline depression, and scar-within the five domains. Central midline depression held the highest weight (16.1 percent) when correlated with global aesthetic rating, followed by semilunar lines (15.8 percent) and infraumbilical skin (11.8 percent). The final scale demonstrated strong validity (Pearson r = 0.99) and was rated as easy to use by seven attending plastic surgeons., Conclusions: The final scale is the first published professional aesthetic scale for the abdomen that aims to integrate layperson opinion. This analysis and survey data provide insights into the importance of 11 components in overall aesthetic appeal of the abdomen., Competing Interests: Disclosure:Dr. Dumanian is a consultant for Checkpoint Surgical and founder of Advanced Suture, Inc., and Mesh Suture, Inc. The authors have no other potential conflicts of interest with respect to the research, authorship, or publication of this article. No funding was received for this article., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Objective: Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered Fibromyalgia Survey Questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA., Methods: Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist, and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included (1) stratified analysis by sex and (2) evaluation of how each component of FSQ associates with the QST measures., Results: Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT ( r range = -0.31 to -0.21), and TS ( r range = 0.13-0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for TS at the wrist and PPT at all sites (except the thumb). Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components., Conclusion: FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization., (Copyright © 2022 by the Journal of Rheumatology.)

Background: Severity of illness scores-Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score, and Sequential Organ Failure Assessment-are current risk stratification and mortality prediction tools used in intensive care units (ICUs) worldwide. Developers of artificial intelligence or machine learning (ML) models predictive of ICU mortality use the severity of illness scores as a reference point when reporting the performance of these computational constructs., Objective: This study aimed to perform a literature review and meta-analysis of articles that compared binary classification ML models with the severity of illness scores that predict ICU mortality and determine which models have superior performance. This review intends to provide actionable guidance to clinicians on the performance and validity of ML models in supporting clinical decision-making compared with the severity of illness score models., Methods: Between December 15 and 18, 2020, we conducted a systematic search of PubMed, Scopus, Embase, and IEEE databases and reviewed studies published between 2000 and 2020 that compared the performance of binary ML models predictive of ICU mortality with the performance of severity of illness score models on the same data sets. We assessed the studies' characteristics, synthesized the results, meta-analyzed the discriminative performance of the ML and severity of illness score models, and performed tests of heterogeneity within and among studies., Results: We screened 461 abstracts, of which we assessed the full text of 66 (14.3%) articles. We included in the review 20 (4.3%) studies that developed 47 ML models based on 7 types of algorithms and compared them with 3 types of the severity of illness score models. Of the 20 studies, 4 (20%) were found to have a low risk of bias and applicability in model development, 7 (35%) performed external validation, 9 (45%) reported on calibration, 12 (60%) reported on classification measures, and 4 (20%) addressed explainability. The discriminative performance of the ML-based models, which was reported as AUROC, ranged between 0.728 and 0.99 and between 0.58 and 0.86 for the severity of illness score-based models. We noted substantial heterogeneity among the reported models and considerable variation among the AUROC estimates for both ML and severity of illness score model types., Conclusions: ML-based models can accurately predict ICU mortality as an alternative to traditional scoring models. Although the range of performance of the ML models is superior to that of the severity of illness score models, the results cannot be generalized due to the high degree of heterogeneity. When presented with the option of choosing between severity of illness score or ML models for decision support, clinicians should select models that have been externally validated, tested in the practice environment, and updated to the patient population and practice environment., Trial Registration: PROSPERO CRD42021203871; https://tinyurl.com/28v2nch8., (©Cristina Barboi, Andreas Tzavelis, Lutfiyya NaQiyba Muhammad. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 31.05.2022.)

Objectives: Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients., Methods: We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ <8 low, FSQ 8-10 moderate and FSQ >10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP., Results: Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]., Conclusion: High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: There are many FDA-approved corticosteroid preparations available for intra-articular injection, however triamcinolone hexacetonide is not one of them. It was the intraarticular drug of choice among pediatric rheumatologists up until approximately a decade ago, when production of this medication ceased. It can be obtained in the United States and Canada via importation from Europe, but it is not FDA-approved at this time. We wish to compare the duration of remission of intraarticular triamcinolone hexacetonide (TH) with that of triamcinolone acetonide (TA) in children with juvenile idiopathic arthritis (JIA) and demonstrate its safety in this population., Methods: This retrospective chart review included 39 patients with JIA who received intraarticular corticosteroid injections (IACIs) from September 2018 to September 2019. These patients were reviewed and their life-time injections with either TH (41 joints) or TA (124 joints) was noted through May 30, 2021. Patients with concomitant systemic therapy initiation were excluded. The primary outcome was time to relapse. Relapse was defined by the presence of arthritis on physical examination by an attending rheumatologist. Kaplan-Meier curves and a log-rank test were constructed to compare the probability of time to relapse between IACI injections. Additionally, mixed effects cox regression models were constructed to account for multiple injections per participant., Results: Kaplan-Meier estimator of median relapse time in months was higher for TH. Based on the log-rank test, TA joints had a higher probability of experiencing a relapse during the study time (p value < 0.001). The hazard of time to relapse was reduced when comparing TH to TA in both unadjusted and adjusted mixed effects cox regression models [unadjusted hazard ratio (95% confidence interval): 0.184 (0.089, 0.381); adjusted hazard ratio (95% confidence interval): 0.189 (0.092, 0.386)]., Conclusions: TH has longer duration of action than TA and is associated with less systemic side effects. It should be considered the drug of choice for intraarticular corticosteroid injections in children with JIA., (© 2022. The Author(s).)

Objective: Develop a model to predict gastrostomy tube (GT) for feeding at discharge in infants born < 30 weeks' (w) gestational age (GA)., Study Design: A single-center retrospective study at academic NICU. Total of 391 (78 GT, 313 non-GT) infants < 30 w GA admitted in 2015-2018 split into test (15-16) and validation (17-18) cohorts. Classification and regression tree analysis was used to identify predictive factors for GT., Results: Several factors were associated with GT requirements. Four factors included in the model were postmenstrual age (PMA) at first oral feeding, birth GA, high-frequency ventilation exposure, necrotizing enterocolitis stage II/III. Area under the receiver operator characteristic curve was 0.944 in the test cohort, 0.815 in the validation cohort. Implementation plan based on the model was developed., Conclusions: We developed a predictive model to risk-stratify infants born < 30 w GA for failing full oral feeding. We hope implementation at 38 w PMA will result in earlier placement of needed GT and discharge., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Clinical case reports circulate relevant information regarding disease presentation and describe treatment protocols, particularly for novel conditions. In the early months of the Covid-19 pandemic, case reports provided key insights into the pathophysiology and sequelae associated with Covid-19 infection and described treatment mechanisms and outcomes. However, case reports are often subject to selection bias due to their singular nature. To better understand how selection biases may have influenced Covid-19-releated case reports, we conducted a bibliometric analysis of Covid-19-releated case reports published in high impact journals from January 1 to June 1, 2020. Case reports were coded for patient sex, country of institutional affiliation, physiological system, and first and last author gender. Of 494 total case reports, 45% ( n = 221) of patients were male, 30% ( n = 146) were female, and 25% ( n = 124) included both sexes. Ratios of male-only to female-only case reports varied by physiological system. The majority of case reports had male first (61%, n = 302) and last (70%, n = 340) authors. Case reports with male last authors were more likely to describe male patients [ X 2 (2, n = 465) = 6.6, p = 0.037], while case reports with female last authors were more likely to include patients of both sexes [OR = 1.918 (95% CI = 1.163-3.16)]. Despite a limited sample size, these data reflect emerging research on sex-differences in the physiological presentation and impact of Covid-19 and parallel large-scale trends in authorship patterns. Ultimately, this work highlights potential biases in the dissemination of clinical information via case reports and underscores the inextricable influences of sex and gender biases within biomedicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Salter-Volz, Oyasu, Yeh, Muhammad and Woitowich.)

Objective: To examine the effects of a smartphone application (app) to monitor longitudinal electronic patient-reported outcomes (ePROs) on patient satisfaction and disease activity in patients with rheumatoid arthritis (RA)., Methods: We conducted a 6-month randomized controlled trial of care coordination along with an app (intervention) versus care coordination alone (control) in 191 RA patients. Participants in the intervention group were prompted to provide information daily using ePROs. In both the intervention and control groups, a care coordinator contacted participants at 6 and 18 weeks to assess for flares. The main outcome measures were the global satisfaction score from the Treatment Satisfaction Questionnaire for Medication (TSQM), the score from the Perceived Efficacy in Patient-Physician Interactions (PEPPI) Questionnaire, and the Clinical Disease Activity Index (CDAI) score., Results: Groups were similar at baseline. The median TSQM score at 6 months was 83.3 in both groups, and the median PEPPI score at 6 months was 50 in both groups. The median CDAI score at 6 months was 8 in the intervention group versus 10 in the control group. No statistically significant group differences in the medians of TSQM, PEPPI, or CDAI scores at 6 months were detected. Of the 67 intervention participants who completed the exit survey, 90% rated their likelihood of recommending the app as ≥7 of 10. Of the 11 physicians who completed the exit survey, 73% agreed/strongly agreed that they wanted to continue offering the app to patients., Conclusion: A mobile app designed to collect ePRO data on RA symptoms did not significantly improve patient satisfaction or disease activity compared to care coordination alone. However, both patients and physicians reported positive experiences with the app., (© 2021, American College of Rheumatology.)

Objective: To determine the association between dysregulated central pain processing and treatment response in rheumatoid arthritis (RA)., Methods: One hundred eighty-two participants with active RA were followed up for 12 weeks after starting a disease-modifying antirheumatic drug (DMARD). To assess central pain processing, participants underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at the trapezius muscles, temporal summation, and conditioned pain modulation (CPM). QST measures were categorized as high central dysregulation versus low central dysregulation. The association between baseline central dysregulation and treatment response, as defined by the European League Against Rheumatism (EULAR) response criteria, was assessed using multiple logistic regression adjusted for demographic characteristics, RA-related variables, and psychosocial variables., Results: A good EULAR response was achieved in fewer participants with high CPM dysregulation than participants with low CPM dysregulation (22.5% versus 40.3%; P = 0.01). A similar trend, though not significant, was noted when central dysregulation was assessed with PPT and temporal summation. The adjusted odds ratios (ORs) for the association between high central dysregulation and good EULAR response were 0.59 for PPTs (95% confidence interval [95% CI] 0.28-1.23), 0.60 for temporal summation (95% CI 0.27-1.34), and 0.40 for CPM (95% CI 0.19-0.83). In a model examining the combined effects of dysregulated temporal summation and CPM, dysregulation of both measures was associated with lower odds of achieving a good EULAR response (OR 0.23 [95% CI 0.07-0.73])., Conclusion: Low CPM was significantly associated with lower odds of achieving a good EULAR response, suggesting that inefficient descending inhibitory mechanisms may be a potential treatment target for further study., (© 2020, American College of Rheumatology.)

Obesity-related type 2 diabetes (DM) is a major public health concern. Adipose tissue metabolic dysfunction, including fibrosis, plays a central role in DM pathogenesis. Obesity is associated with changes in adipose tissue extracellular matrix (ECM), but the impact of these changes on adipose tissue mechanics and their role in metabolic disease is poorly defined. This study utilized atomic force microscopy (AFM) to quantify difference in elasticity between human DM and non-diabetic (NDM) visceral adipose tissue. The mean elastic modulus of DM adipose tissue was twice that of NDM adipose tissue (11.50 kPa vs. 4.48 kPa) to a 95% confidence level, with significant variability in elasticity of DM compared to NDM adipose tissue. Histologic and chemical measures of fibrosis revealed increased hydroxyproline content in DM adipose tissue, but no difference in Sirius Red staining between DM and NDM tissues. These findings support the hypothesis that fibrosis, evidenced by increased elastic modulus, is enhanced in DM adipose tissue, and suggest that measures of tissue mechanics may better resolve disease-specific differences in adipose tissue fibrosis compared with histologic measures. These data demonstrate the power of AFM nanoindentation to probe tissue mechanics, and delineate the impact of metabolic disease on the mechanical properties of adipose tissue.

Background: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established., Objective: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use., Methods: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCR-confirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization., Results: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15)., Conclusions: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization., (Copyright © 2020. Published by Elsevier Inc.)

Background: Positive associations between suicidal behaviors and asthma have been established in previous adolescent studies. Few studies consider social risk factors, such as bullying. This study involved an analysis of suicidal behaviors and asthma, but also includes an assessment of whether these relationships were modified by the co-occurrence of bullying., Methods: Data included 13,154 participants from the 2013 Youth Risk Behavior Survey (YRBS), collected by the US Centers for Disease Control and Prevention. Logistic regression models were constructed and summarized using odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: When comparing adolescents with asthma who were bullied at school to those who were not bullied at school, the odds of contemplating suicide were increased by nearly 2-fold (OR = 1.8, 95% CI = 1.5-2.3), and the odds of creating a suicide plan were 2.3 times higher (OR = 2.3, 95% CI = 1.7-3.1). The odds of a suicide attempt and incurring an injury from a suicide attempt were also substantially increased. Similarly, increased odds of suicidal behaviors were observed for adolescents with asthma who were bullied electronically., Conclusion: Having asthma and being bullied are both associated with increased odds of suicidal behaviors., (© 2018, American School Health Association.)

Background: As statisticians develop new methodological approaches, there are many factors that influence whether others will utilize their work. This paper is a bibliometric study that identifies and quantifies associations between characteristics of new biostatistics methods and their citation counts. Of primary interest was the association between numbers of citations and whether software code was available to the reader., Methods: Statistics journal articles published in 2010 from 35 statistical journals were reviewed by two biostatisticians. Generalized linear mixed models were used to determine which characteristics (author, article, and journal) were independently associated with citation counts (as of April 1, 2017) in other peer-reviewed articles., Results: Of 722 articles reviewed, 428 were classified as new biostatistics methods. In a multivariable model, for articles that were not freely accessible on the journal's website, having code available appeared to offer no boost to the number of citations (adjusted rate ratio = 0.96, 95% CI = 0.74 to 1.24, p = 0.74); however, for articles that were freely accessible on the journal's website, having code available was associated with a 2-fold increase in the number of citations (adjusted rate ratio = 2.01, 95% CI = 1.30 to 3.10, p = 0.002). Higher citation rates were also associated with higher numbers of references, longer articles, SCImago Journal Rank indicator (SJR), and total numbers of publications among authors, with the strongest impact on citation rates coming from SJR (rate ratio = 1.21 for a 1-unit increase in SJR; 95% CI = 1.11 to 1.32)., Conclusion: These analyses shed new insight into factors associated with citation rates of articles on new biostatistical methods. Making computer code available to readers is a goal worth striving for that may enhance biostatistics knowledge translation., Competing Interests: The authors have declared that no competing interests exist.