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153. Physical Activity and Correlates of Physical Activity Participation Over Three Years in Adults with Rheumatoid Arthritis

Author

Iversen, Maura D, Frits, Michelle, von Heideken, Johan, Cui, Jing, Weinblatt, Michael, and Shadick, Nancy A

Subjects
Adult, Male, Health Knowledge, Attitudes, Practice, Time Factors, Adolescent, Health Status, Severity of Illness Index, Article, Arthritis, Rheumatoid, Young Adult, Risk Factors, Odds Ratio, Humans, Longitudinal Studies, Registries, Exercise, Life Style, Aged, Middle Aged, Prognosis, Logistic Models, Mental Health, Multivariate Analysis, Female, Perception, Self Report
Abstract

To characterize physical activity participation (moderate-to-vigorous physical activity [MVPA], ≥150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week), to examine associations between disease activity and MVPA, and to identify MVPA correlates in adults with rheumatoid arthritis (RA) over 3 years.This study included 573 RA patients (94% white, 83% female, mean age 61 years, mean RA duration 19.5 years) with ≥1 annual registry visit and who completed the physical activity questionnaire. Baseline and annual measures included demographics/medical history, self-efficacy for disease management, quality of life, patient/physician global assessment, physical function, and self-reported physical activity. A logistic repeated-measures model using the generalized estimating equation examined the relationship between disease activity and MVPA.Average disease activity (from the 3-variable Disease Activity Score in 28 joints using the C-reactive protein level) was mean ± SD 3.1 ± 1.4, 36% were physically inactive, and 29% met MVPA recommendations. There was a negative borderline association with disease activity (odds ratio [OR] 0.89 [95% confidence interval (95% CI) 0.79-1.00]). Correlates of meeting MVPA recommendations, adjusting for disease activity, were being white (OR 2.95 [95% CI 1.29-6.75]), older age (ages69 years OR 0.58 [95% CI 0.36-0.92]), poor mental health (OR 0.63 [95% CI 0.41-0.95]), poor physical function (OR 0.59 [95% CI 0.34-1.01]), overweight/obese (body mass index [BMI]25-30 OR 0.69 [95% CI 0.50-0.95], BMI30-39.9 OR 0.60 [95% CI 0.41-0.88], and BMI ≤40 OR 0.24 [95% CI 0.08-0.74]), and patient global assessment (≥10-20 OR 0.57 [95% CI 0.39-0.83]).A small proportion of patients met MVPA recommendations despite well-controlled disease. Disease activity was negatively associated with physical activity over time. Physical activity correlates were linked to lifestyle, mental health, and patient perceptions of disease, suggesting physical activity interventions that address patient perspectives may facilitate RA management.

Published
2017

155. Additional file 1: Table S1. of Drug safety analyses in a rheumatoid arthritis registry: application of different approaches regarding timing of exposure and confounder measurement

Author

Solomon, Daniel, Shadick, Nancy, Weinblatt, Michael, Zak, Agnes, Frits, Michelle, and Franklin, Jessica

Subjects
animal structures, viruses
Abstract

Baseline characteristics of subjects prior to trimming. Table describing baseline characteristics of subjects prior to trimming. (DOCX 13 kb)

Published
2017
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156. Additional file 2: Figure S1. of Drug safety analyses in a rheumatoid arthritis registry: application of different approaches regarding timing of exposure and confounder measurement

Author

Solomon, Daniel, Shadick, Nancy, Weinblatt, Michael, Zak, Agnes, Frits, Michelle, and Franklin, Jessica

Subjects
musculoskeletal diseases, immune system diseases, sense organs, skin and connective tissue diseases
Abstract

Change in DAS28-CRP between visits before and after start of treatment. Figure describing change in DAS28-CRP. (DOCX 463 kb)

Published
2017
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158. Supporting Wellness, Resilience, and Community With Forest Therapy

Author

Abookire, Susan A, Ayala, Sujata G, and Shadick, Nancy A

Abstract

Background Physician burnout has reached epidemic proportions. Although burnout is rooted in systems, practices for physician wellbeing and community can address exhaustion, burnout, and isolation. Inspired by the Japanese practice shinrin-yoku, forest therapy/bathing (FT) is a nature immersion practice that improves wellbeing in a group setting.Objective This program offered guided FT experiences to frontline faculty physicians in the Department of Medicine and evaluated potential for impact on burnout, resilience, and community.Methods Faculty physicians were recruited via email invitations to a free Forest Therapy group experience in the Arnold Arboretum in Boston, MA. Participants completed pre-and post-course surveys and evaluated its value as a community experience. Surveys measured burnout, resilience, and qualitative feedback on the experience.Results Twenty-seven faculty completed the baseline survey, twenty-three faculty participated, with 19 survey respondents. At baseline, 85% reported feeling burned out at least once a month. 46% reported feeling burned out more than a few times a month. 83% of participants responded that forest therapy could help them with the feeling of being burned out from work. Post-intervention, 100% of participants rated the experience as very or extremely valuable. 96% of participants reported they were interested in more frequent forest therapy sessions. 100% of participants would recommend this practice to other faculty. 70% of respondents reported the program could help them with burnout. Despite high baseline resilience, 94% of participants reported that forest therapy could help with stressful events and setbacks. Post-intervention, participants reported feeling relaxed, at peace, and calm.Conclusion This pilot demonstrates feasibility and acceptability for physicians of FT. Participants would consider recommending FT to their colleagues, and agreed that FT can help with wellbeing, and expressed enthusiasm for the community experience. This program may also be successfully incorporated into programs for leadership, teambuilding, and support after adverse events.

Published
2024
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161. Development of a Molecular Signature to Monitor Pharmacodynamic Responses Mediated by In Vivo Administration of Glucocorticoids

Author

Hu, Yanhua, primary, Carman, Julie A., additional, Holloway, Deborah, additional, Kansal, Selena, additional, Fan, Li, additional, Goldstine, Christine, additional, Lee, Deborah, additional, Somerville, John E., additional, Latek, Robert, additional, Townsend, Robert, additional, Johnsen, Alyssa, additional, Connolly, Sean, additional, Bandyopadhyay, Somnath, additional, Shadick, Nancy, additional, Weinblatt, Michael E., additional, Furie, Richard, additional, and Nadler, Steven G., additional

Published
2018
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162. Morphological Variables Associated With Ruptured Middle Cerebral Artery Aneurysms

Author

Zhang, Jian, primary, Can, Anil, additional, Mukundan, Srinivasan, additional, Steigner, Michael, additional, Castro, Victor M, additional, Dligach, Dmitriy, additional, Finan, Sean, additional, Yu, Sheng, additional, Gainer, Vivian, additional, Shadick, Nancy A, additional, Savova, Guergana, additional, Murphy, Shawn, additional, Cai, Tianxi, additional, Wang, Zhong, additional, Weiss, Scott T, additional, and Du, Rose, additional

Published
2018
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166. Heroin Use Is Associated with Ruptured Saccular Aneurysms

Author

Can, Anil, primary, Castro, Victor M., additional, Ozdemir, Yildirim H., additional, Dagen, Sarajune, additional, Dligach, Dmitriy, additional, Finan, Sean, additional, Yu, Sheng, additional, Gainer, Vivian, additional, Shadick, Nancy A., additional, Savova, Guergana, additional, Murphy, Shawn, additional, Cai, Tianxi, additional, Weiss, Scott T., additional, and Du, Rose, additional

Published
2017
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167. Development of an Adjusted Multi-Biomarker Disease Activity (MBDA) Score for Rheumatoid Arthritis (RA) That Accounts for Age, Sex and Adiposity, with Subsequent Evaluation of Ability to Predict Risk for Radiographic Damage

Author

Curtis, Jeffrey R, Flake II, Darl D, Weinblatt, Michael E., Shadick, Nancy A., Østergaard, Mikkel, Hetland, Merete Lund, Brahe, Cecilie Heegaard, Hwang, Yong Gil, Furst, Daniel E, Strand, Vibeke, Etzel, Carol J., Pappas, Dimitrios A., Wang, Xingbin, Hwang, Ching Chang, Sasso, Eric H, Gutin, Alexander, Hitraya, Elena, Lanchbury, Jerry S., Curtis, Jeffrey R, Flake II, Darl D, Weinblatt, Michael E., Shadick, Nancy A., Østergaard, Mikkel, Hetland, Merete Lund, Brahe, Cecilie Heegaard, Hwang, Yong Gil, Furst, Daniel E, Strand, Vibeke, Etzel, Carol J., Pappas, Dimitrios A., Wang, Xingbin, Hwang, Ching Chang, Sasso, Eric H, Gutin, Alexander, Hitraya, Elena, and Lanchbury, Jerry S.

Published
2017

172. Different Rating of Global Rheumatoid Arthritis Disease Activity in Rheumatoid Arthritis Patients With Multiple Morbidities

Author

Radner, Helga, primary, Yoshida, Kazuki, additional, Tedeschi, Sara, additional, Studenic, Paul, additional, Frits, Michelle, additional, Iannaccone, Christine, additional, Shadick, Nancy A., additional, Weinblatt, Michael, additional, Aletaha, Daniel, additional, Smolen, Josef S., additional, and Solomon, Daniel H., additional

Published
2017
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173. Large-scale identification of patients with cerebral aneurysms using natural language processing

Author

Castro, Victor M., primary, Dligach, Dmitriy, additional, Finan, Sean, additional, Yu, Sheng, additional, Can, Anil, additional, Abd-El-Barr, Muhammad, additional, Gainer, Vivian, additional, Shadick, Nancy A., additional, Murphy, Shawn, additional, Cai, Tianxi, additional, Savova, Guergana, additional, Weiss, Scott T., additional, and Du, Rose, additional

Published
2016
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175. Utilizing biologic disease-modifying anti-rheumatic treatment sequences to subphenotype rheumatoid arthritis

Author

Das, Priyam, Weisenfeld, Dana, Dahal, Kumar, De, Debsurya, Feathers, Vivi, Coblyn, Jonathan S., Weinblatt, Michael E., Shadick, Nancy A., Cai, Tianxi, and Liao, Katherine P.

Abstract

Background: Many patients with rheumatoid arthritis (RA) require a trial of multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) to control their disease. With the availability of several bDMARD options, the history of bDMARDs may provide an alternative approach to understanding subphenotypes of RA. The objective of this study was to determine whether there exist distinct clusters of RA patients based on bDMARD prescription history to subphenotype RA. Methods: We studied patients from a validated electronic health record-based RA cohort with data from January 1, 2008, through July 31, 2019; all subjects prescribed ≥ 1 bDMARD or targeted synthetic (ts) DMARD were included. To determine whether subjects had similar b/tsDMARD sequences, the sequences were considered as a Markov chain over the state-space of 5 classes of b/tsDMARDs. The maximum likelihood estimator (MLE)-based approach was used to estimate the Markov chain parameters to determine the clusters. The EHR data of study subjects were further linked with a registry containing prospectively collected data for RA disease activity, i.e., clinical disease activity index (CDAI). As a proof of concept, we tested whether the clusters derived from b/tsDMARD sequences correlated with clinical measures, specifically differing trajectories of CDAI. Results: We studied 2172 RA subjects, mean age 52 years, RA duration 3.4 years, and 62% seropositive. We observed 550 unique b/tsDMARD sequences and identified 4 main clusters: (1) TNFi persisters (65.7%), (2) TNFi and abatacept therapy (8.0%), (3) on rituximab or multiple b/tsDMARDs (12.7%), (4) prescribed multiple therapies with tocilizumab predominant (13.6%). Compared to the other groups, TNFi persisters had the most favorable trajectory of CDAI over time. Conclusion: We observed that RA subjects can be clustered based on the sequence of b/tsDMARD prescriptions over time and that the clusters were correlated with differing trajectories of disease activity over time. This study highlights an alternative approach to consider subphenotyping of patients with RA for studies aimed at understanding treatment response.

Published
2023
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176. Association of hemoglobin levels with radiographic progression in patients with rheumatoid arthritis: an analysis from the BRASS registry

Author

Shadick, Nancy, Hagino, Owen, Praestgaard, Amy, Fiore, Stefano, Weinblatt, Michael, and Burmester, Gerd

Abstract

Background: To evaluate baseline hemoglobin (Hb) and radiographic progression over time in patients enrolled in the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS) registry. Methods: The BRASS is a prospective observational registry of patients with rheumatoid arthritis. BRASS Hb data and total sharp score data were matched with the main BRASS patients. Hb at baseline was categorized per the World Health Organization guidelines. Mean Hb, mean total sharp score, and mean changes over time from baseline to month 120 were summarized (overall, by low/normal Hb, and by current medication at baseline). All analyses were descriptive. Results: Out of the total (N= 1114) rheumatoid arthritis patients included in the analysis, patients with low Hb at baseline (n= 224 [20%]) had longer disease duration and higher disease activity and reported more pain compared with patients with normal Hb at baseline (n= 890 [80%]). Patients with low Hb at baseline continued to have lower Hb than patients with normal Hb throughout 10 years; although, on average, patients in the low Hb subgroup exhibited a steady increase in Hb levels. A larger increase in total sharp score over time was observed for patients with low Hb than for patients with normal Hb. No meaningful differences potentially attributable to medication at baseline were detected. Conclusions: Patients with low Hb levels at baseline tended to have increased radiographic progression as measured by total sharp score compared with patients with rheumatoid arthritis having normal Hb levels. Patients with low Hb experienced sustained improvements in Hb levels over time, regardless of the class of medication used. Trial registration: ClinicalTrials.gov NCT01793103.

Published
2023
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177. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

Author

University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Mathematics and Statistics, University of Helsinki, Department of Computer Science, Sieberts, Solveig K., Zhu, Fan, Garcia-Garcia, Javier, Stahl, Eli, Pratap, Abhishek, Pandey, Gaurav, Pappas, Dimitrios, Aguilar, Daniel, Anton, Bernat, Bonet, Jaume, Eksi, Ridvan, Fornes, Oriol, Guney, Emre, Li, Hongdong, Marin, Manuel Alejandro, Panwar, Bharat, Planas-Iglesias, Joan, Poglayen, Daniel, Cui, Jing, Falcao, Andre O., Suver, Christine, Hoff, Bruce, Balagurusamy, Venkat S. K., Dillenberger, Donna, Neto, Elias Chaibub, Norman, Thea, Aittokallio, Tero, Ammad-ud-din, Muhammad, Azencott, Chloe-Agathe, Bellon, Victor, Boeva, Valentina, Bunte, Kerstin, Chheda, Himanshu, Cheng, Lu, Corander, Jukka, Dumontier, Michel, Goldenberg, Anna, Gopalacharyulu, Peddinti, Hajiloo, Mohsen, Hidru, Daniel, Jaiswal, Alok, Kaski, Samuel, Khalfaoui, Beyrem, Khan, Suleiman Ali, Kramer, Eric R., Marttinen, Pekka, Mezlini, Aziz M., Molparia, Bhuvan, Pirinen, Matti, Saarela, Janna, Samwald, Matthias, Stoven, Veronique, Tang, Hao, Tang, Jing, Torkamani, Ali, Vert, Jean-Phillipe, Wang, Bo, Wang, Tao, Wennerberg, Krister, Wineinger, Nathan E., Xiao, Guanghua, Xie, Yang, Yeung, Rae, Zhan, Xiaowei, Zhao, Cheng, Greenberg, Jeff, Kremer, Joel, Michaud, Kaleb, Barton, Anne, Coenen, Marieke, Mariette, Xavier, Miceli, Corinne, Shadick, Nancy, Weinblatt, Michael, de Vries, Niek, Tak, Paul P., Gerlag, Danielle, Huizinga, Tom W. J., Kurreeman, Fina, Allaart, Cornelia F., Bridges, S. Louis, Criswell, Lindsey, Moreland, Larry, Klareskog, Lars, Saevarsdottir, Saedis, Padyukov, Leonid, Gregersen, Peter K., Friend, Stephen, Plenge, Robert, Stolovitzky, Gustavo, Oliva, Baldo, Guan, Yuanfang, Mangravite, Lara M., Rheumatoid Arth Challenge, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Department of Mathematics and Statistics, University of Helsinki, Department of Computer Science, Sieberts, Solveig K., Zhu, Fan, Garcia-Garcia, Javier, Stahl, Eli, Pratap, Abhishek, Pandey, Gaurav, Pappas, Dimitrios, Aguilar, Daniel, Anton, Bernat, Bonet, Jaume, Eksi, Ridvan, Fornes, Oriol, Guney, Emre, Li, Hongdong, Marin, Manuel Alejandro, Panwar, Bharat, Planas-Iglesias, Joan, Poglayen, Daniel, Cui, Jing, Falcao, Andre O., Suver, Christine, Hoff, Bruce, Balagurusamy, Venkat S. K., Dillenberger, Donna, Neto, Elias Chaibub, Norman, Thea, Aittokallio, Tero, Ammad-ud-din, Muhammad, Azencott, Chloe-Agathe, Bellon, Victor, Boeva, Valentina, Bunte, Kerstin, Chheda, Himanshu, Cheng, Lu, Corander, Jukka, Dumontier, Michel, Goldenberg, Anna, Gopalacharyulu, Peddinti, Hajiloo, Mohsen, Hidru, Daniel, Jaiswal, Alok, Kaski, Samuel, Khalfaoui, Beyrem, Khan, Suleiman Ali, Kramer, Eric R., Marttinen, Pekka, Mezlini, Aziz M., Molparia, Bhuvan, Pirinen, Matti, Saarela, Janna, Samwald, Matthias, Stoven, Veronique, Tang, Hao, Tang, Jing, Torkamani, Ali, Vert, Jean-Phillipe, Wang, Bo, Wang, Tao, Wennerberg, Krister, Wineinger, Nathan E., Xiao, Guanghua, Xie, Yang, Yeung, Rae, Zhan, Xiaowei, Zhao, Cheng, Greenberg, Jeff, Kremer, Joel, Michaud, Kaleb, Barton, Anne, Coenen, Marieke, Mariette, Xavier, Miceli, Corinne, Shadick, Nancy, Weinblatt, Michael, de Vries, Niek, Tak, Paul P., Gerlag, Danielle, Huizinga, Tom W. J., Kurreeman, Fina, Allaart, Cornelia F., Bridges, S. Louis, Criswell, Lindsey, Moreland, Larry, Klareskog, Lars, Saevarsdottir, Saedis, Padyukov, Leonid, Gregersen, Peter K., Friend, Stephen, Plenge, Robert, Stolovitzky, Gustavo, Oliva, Baldo, Guan, Yuanfang, Mangravite, Lara M., and Rheumatoid Arth Challenge

Abstract

Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in Bone-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2) = 0.18, P value = 0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.

Published
2016

178. Subgrouping of rheumatoid arthritis patients based on pain, fatigue, inflammation and psychosocial factors

Author

Lee, Yvonne C., Frits, Michelle L., Iannaccone, Christine K., Weinblatt, Michael E., Shadick, Nancy A., Williams, David A., and Cui, Jing

Subjects
Arthritis, Rheumatoid, Inflammation, Male, Humans, Pain, Female, Prospective Studies, Middle Aged, Article, Fatigue, Aged
Abstract

Among patients with rheumatoid arthritis (RA), pain may be attributed to peripheral inflammation or other causes, such as central pain mechanisms. The aim of this study was to use self-report measures and physical examination findings to identify clusters of RA patients who may have different causes of pain as well as different prognoses and treatment options.Data from 169 RA patients with pain scores of0 (on a 10-point numeric rating scale) in the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study were analyzed. The patients completed questionnaires on pain, fatigue, and psychosocial factors. A hierarchical agglomerative clustering procedure with Ward's method was used to obtain subgroups. Multivariate analysis of variance was used to determine the contribution of each variable in a cluster. General linear regression models were used to examine differences in clinical characteristics across subgroups. Discriminant analyses were performed to determine coefficients for linear combinations of variables that assigned cluster membership to individual cases.Three clusters best fit these data. Cluster 1 consisted of 89 individuals with low levels of inflammation, pain, fatigue, and psychosocial distress. Cluster 2 consisted of 57 individuals with minimal inflammation but high levels of pain, fatigue, and psychosocial distress. Cluster 3 consisted of 23 individuals with active inflammatory disease, manifested by high swollen joint counts, high C-reactive protein levels, and high levels of pain and fatigue.Although most patients had low levels of inflammation, pain, and fatigue, 47.3% continued to report having moderate to high levels of pain and fatigue. Most of these patients had minimal signs of inflammation but high levels of fatigue, pain catastrophizing, and sleep disturbance, indicative of a chronic widespread pain syndrome.

Published
2014

181. Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

Author

Alemao, Evo, primary, Joo, Seongjung, additional, Kawabata, Hugh, additional, Al, Maiwenn J., additional, Allison, Paul D., additional, Rutten‐van Mölken, Maureen P. M. H., additional, Frits, Michelle L., additional, Iannaccone, Christine K., additional, Shadick, Nancy A., additional, and Weinblatt, Michael E., additional

Published
2016
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184. Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis

Author

Wampler Muskardin, Theresa, primary, Vashisht, Priyanka, additional, Dorschner, Jessica M, additional, Jensen, Mark A, additional, Chrabot, Beverly S, additional, Kern, Marlena, additional, Curtis, Jeffrey R, additional, Danila, Maria I, additional, Cofield, Stacey S, additional, Shadick, Nancy, additional, Nigrovic, Peter A, additional, St Clair, E William, additional, Bingham, Clifton O, additional, Furie, Richard, additional, Robinson, William, additional, Genovese, Mark, additional, Striebich, Christopher C, additional, O'Dell, James R, additional, Thiele, Geoffrey M, additional, Moreland, Larry W, additional, Levesque, Marc, additional, Bridges, S Louis, additional, Gregersen, Peter K, additional, and Niewold, Timothy B, additional

Published
2015
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188. Heroin Use Is Associated with Ruptured Saccular Aneurysms.

Author

Can, Anil, Castro, Victor M., Ozdemir, Yildirim H., Dagen, Sarajune, Dligach, Dmitriy, Finan, Sean, Yu, Sheng, Gainer, Vivian, Shadick, Nancy A., Savova, Guergana, Murphy, Shawn, Cai, Tianxi, Weiss, Scott T., and Du, Rose

Abstract

While cocaine use is thought to be associated with aneurysmal rupture, it is not known whether heroin use increases the risk of rupture in patients with non-mycotic saccular aneurysms. Our goal was to investigate the association between heroin and cocaine use and the rupture of saccular non-mycotic aneurysms. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and non-ruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the association between heroin, cocaine, and methadone use and the presence of ruptured intracranial aneurysms. In multivariable analysis, current heroin use was significantly associated with rupture status (OR 3.23, 95% CI 1.33-7.83) whereas former heroin use (with and without methadone replacement therapy), and current and former cocaine use were not significantly associated with intracranial aneurysm rupture. In the present study, heroin rather than cocaine use is significantly associated with intracranial aneurysm rupture in patients with non-mycotic saccular cerebral aneurysms, emphasizing the possible role of heroin in the pathophysiology of aneurysm rupture and the importance of heroin cessation in patients harboring unruptured intracranial aneurysms. [ABSTRACT FROM AUTHOR]

Published
2018
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189. Development of a Molecular Signature to Monitor Pharmacodynamic Responses Mediated by In Vivo Administration of Glucocorticoids.

Author

Nadler, Steven G., Hu, Yanhua, Carman, Julie A., Holloway, Deborah, Kansal, Selena, Fan, Li, Goldstine, Christine, Lee, Deborah, Somerville, John E., Latek, Robert, Townsend, Robert, Johnsen, Alyssa, Connolly, Sean, Bandyopadhyay, Somnath, Shadick, Nancy, Weinblatt, Michael E., and Furie, Richard

Subjects
ALGORITHMS, BIOMARKERS, CELL receptors, DRUG monitoring, GLUCOCORTICOIDS, LEUCOCYTES, NEUTROPHILS, ORAL drug administration, RHEUMATOID arthritis, SYSTEMIC lupus erythematosus, GENE expression profiling, PREDNISOLONE, IN vivo studies
Abstract

Objective: To develop an objective, readily measurable pharmacodynamic biomarker of glucocorticoid (GC) activity. Methods: Genes modulated by prednisolone were identified from in vitro studies using peripheral blood mononuclear cells from normal healthy volunteers. Using the criteria of a >2‐fold change relative to vehicle controls and an adjusted P value cutoff of less than 0.05, 64 up‐regulated and 18 down‐regulated genes were identified. A composite score of the up‐regulated genes was generated using a single‐sample gene set enrichment analysis algorithm. Results: GC gene signature expression was significantly elevated in peripheral blood leukocytes from normal healthy volunteers following oral administration of prednisolone. Expression of the signature increased in a dose‐dependent manner, peaked at 4 hours postadministration, and returned to baseline levels by 48 hours after dosing. Lower expression was detected in normal healthy volunteers who received a partial GC receptor agonist, which is consistent with the reduced transactivation potential of this compound. In cohorts of patients with systemic lupus erythematosus and patients with rheumatoid arthritis, expression of the GC signature was negatively correlated with the percentages of peripheral blood lymphocytes and positively correlated with peripheral blood neutrophil counts, which is consistent with the known biology of the GC receptor. Expression of the signature largely agreed with reported GC use in these populations, although there was significant interpatient variability within the dose cohorts. Conclusion: The GC gene signature identified in this study represents a pharmacodynamic marker of GC exposure. [ABSTRACT FROM AUTHOR]

Published
2018
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192. Alcohol Consumption and Aneurysmal Subarachnoid Hemorrhage.

Author

Can, Anil, Castro, Victor, Ozdemir, Yildirim, Dagen, Sarajune, Dligach, Dmitriy, Finan, Sean, Yu, Sheng, Gainer, Vivian, Shadick, Nancy, Savova, Guergana, Murphy, Shawn, Cai, Tianxi, Weiss, Scott, and Du, Rose

Abstract

Alcohol consumption may be a modifiable risk factor for rupture of intracranial aneurysms. Our aim is to evaluate the association between ruptured aneurysms and alcohol consumption, intensity, and cessation. The medical records of 4701 patients with 6411 radiographically confirmed intracranial aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms. Univariable and multivariable logistic regression analyses were performed to determine the association between alcohol consumption and rupture of intracranial aneurysms. In multivariable analysis, current alcohol use (OR 1.36, 95% CI 1.17-1.58) was associated with rupture status compared with never drinkers, whereas former alcohol use was not significant (OR 1.23, 95% CI 0.92-1.63). In addition, the number of alcoholic beverages per day among current alcohol users (OR 1.13, 95% CI 1.04-1.23) was significantly associated with rupture status, whereas alcohol use intensity was not significant among former users (OR 1.02, 95% CI 0.94-1.11). Current alcohol use and intensity are significantly associated with intracranial aneurysm rupture. However, this increased risk does not persist in former alcohol users, emphasizing the potential importance of alcohol cessation in patients harboring unruptured aneurysms. [ABSTRACT FROM AUTHOR]

Published
2018
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193. Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort.

Author

Ahmad, Harris A., Alemao, Evo, Guo, Zhenchao, Iannaccone, Christine K., Frits, Michelle L., Weinblatt, Michael, and Shadick, Nancy A.

Subjects
COMPARATIVE studies, DIAGNOSTIC imaging, EXPERIMENTAL design, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RHEUMATOID arthritis, EVALUATION research, BONE density, POSTMENOPAUSE
Abstract

Introduction: To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).Methods: Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR-BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2-immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1-3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.Results: A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [-], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2- group. DXR-BMD was lower in the anti-CCP2+ vs. the anti-CCP2- groups (Gp1-3 vs. anti-CCP2-: P < 0.0001 for left and right hands). DXR-BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR-BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).Conclusion: Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.Funding: Bristol-Myers Squibb.Trial Registration: Clinicaltrials.gov identifier, NCT01793103. [ABSTRACT FROM AUTHOR]

Published
2018
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195. Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases

Author

Herman, Jonathan D., Atyeo, Caroline, Zur, Yonatan, Cook, Claire E., Patel, Naomi J., Vanni, Kathleen M., Kowalski, Emily N., Qian, Grace, Srivatsan, Shruthi, Shadick, Nancy A., Rao, Deepak A., Kellman, Benjamin, Mann, Colin J., Lauffenburger, Douglas, Wallace, Zachary S., Sparks, Jeffrey A., and Alter, Galit

Abstract

Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2– or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti–SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs.

Published
2023
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196. Development of a multimorbidity index: Impact on quality of life using a rheumatoid arthritis cohort

Author

Radner, Helga, primary, Yoshida, Kazuki, additional, Mjaavatten, Maria Dahl, additional, Aletaha, Daniel, additional, Frits, Michelle, additional, Lu, Bing, additional, Iannaccone, Christine, additional, Shadick, Nancy, additional, Weinblatt, Michael, additional, Hmamouchi, Ihsane, additional, Dougados, M., additional, Smolen, Josef. S, additional, and Solomon, Daniel. H, additional

Published
2015
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197. IgG galactosylation aberrancy precedes disease onset, correlates with disease activity and is prevalent in autoantibodies in rheumatoid arthritis

Author

Ercan, Altan, Cui, Jing, Chatterton, Dereck E.W., Deane, Kevin D., Hazen, Melissa M., Brintnell, William, O’Donnell, Colin I., Derber, Lezlie A., Weinblatt, Michael E., Shadick, Nancy A., Bell, David A., Cairns, Ewa, Solomon, Daniel H., Holers, V. Michael, Rudd, Pauline M., and Lee, David M.

Subjects
Arthritis, Rheumatoid, Male, C-Reactive Protein, Sex Factors, Polysaccharides, Immunoglobulin G, Humans, Female, Middle Aged, Severity of Illness Index, Article, Autoantibodies
Abstract

To examine the association between aberrant IgG galactosylation and disease parameters in rheumatoid arthritis (RA).Analysis of N-glycan in serum samples from multiple cohorts was performed. The IgG N-glycan content and the timing of N-glycan aberrancy relative to disease onset were compared in healthy subjects and in patients with RA. Correlations between aberrant galactosylation and disease activity were assessed in the RA cohorts. The impact of disease activity, sex, age, anti-cyclic citrullinated peptide (anti-CCP) antibody titer, disease duration, and C-reactive protein level on aberrant galactosylation was determined using multivariate analysis. The N-glycan content was also compared between epitope affinity-purified autoantibodies and the remaining IgG repertoire in RA patients.Our results confirm the aberrant galactosylation of IgG in RA patients as compared with healthy controls (mean +/- SD 1.36 +/- 0.43 versus 1.01 +/- 0.23; P0.0001). We observed a significant correlation between levels of aberrant IgG galactosylation and disease activity (Spearman's rho = 0.37, P0.0001). This correlation was higher in women (Spearman's rho = 0.60, P0.0001) than in men (Spearman's rho = 0.16, P = 0.10). Further, aberrant IgG galactosylation substantially predated the onset of arthritis and the diagnosis of RA (3.5 years) and resided selectively in the anticitrullinated antigen fraction.Our findings identify aberrant IgG galactosylation as a dysregulated component of the humoral immune response in RA that begins prior to disease onset, associates with disease activity in a sex-specific manner, and resides preferentially in autoantibodies.

Published
2010

199. Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

Author

Doyle, Tracy J., primary, Patel, Avignat S., additional, Hatabu, Hiroto, additional, Nishino, Mizuki, additional, Wu, Guodong, additional, Osorio, Juan C., additional, Golzarri, Maria F., additional, Traslosheros, Andres, additional, Chu, Sarah G., additional, Frits, Michelle L., additional, Iannaccone, Christine K., additional, Koontz, Diane, additional, Fuhrman, Carl, additional, Weinblatt, Michael E., additional, El-Chemaly, Souheil Y., additional, Washko, George R., additional, Hunninghake, Gary M., additional, Choi, Augustine M. K., additional, Dellaripa, Paul F., additional, Oddis, Chester V., additional, Shadick, Nancy A., additional, Ascherman, Dana P., additional, and Rosas, Ivan O., additional

Published
2015
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