المؤلفون: Kumara, Mahima T., Cleveland, Rebecca J., Kostic, Aleksandra M., Weisner, Serena E., Allen, Kelli D., Golightly, Yvonne M., Welch, Heather, Dale, Melissa, Messier, Stephen P., Hunter, David J., Katz, Jeffrey N., Callahan, Leigh F., Losina, Elena

المساهمون: CDC, National Institute of Arthritis and Musculoskeletal and Skin Diseases

المصدر: Osteoarthritis and Cartilage Open ; volume 6, issue 2, page 100463 ; ISSN 2665-9131

مصطلحات موضوعية: General Medicine

الإتاحة: https://doi.org/10.1016/j.ocarto.2024.100463Test
https://api.elsevier.com/content/article/PII:S266591312400030X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S266591312400030X?httpAccept=text/plainTest

المؤلفون: Yang, Kyungae, Mitchell, Noelle M., Banerjee, Saswata, Cheng, Zhenzhuang, Taylor, Steven, Kostic, Aleksandra M., Wong, Isabel, Sajjath, Sairaj, Zhang, Yameng, Stevens, Jacob, Mohan, Sumit, Landry, Donald W., Worgall, Tilla S., Andrews, Anne M., Stojanovic, Milan N.

المصدر: Science, 380(6648), 942-948, (2023-06-02)

مصطلحات موضوعية: Multidisciplinary

الوصف: Aptameric receptors are important biosensor components, yet our ability to identify them depends on the target structures. We analyzed the contributions of individual functional groups on small molecules to binding within 27 target-aptamer pairs, identifying potential hindrances to receptor isolation—for example, negative cooperativity between sterically hindered functional groups. To increase the probability of aptamer isolation for important targets, such as leucine and voriconazole, for which multiple previous selection attempts failed, we designed tailored strategies focused on overcoming individual structural barriers to successful selections. This approach enables us to move beyond standardized protocols into functional group–guided searches, relying on sequences common to receptors for targets and their analogs to serve as anchors in regions of vast oligonucleotide spaces wherein useful reagents are likely to be found. ; © 2023 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. We thank B. Solaja, F. Katz, H. Hess, D. Stefanović, S. Rudchenko, A. K. Rinderspacher, C. Boyle, V. Cornish, and J. Loeb for their input during the writing of this manuscript. We thank S. Deng and A. K. Rinderspacher for helping Z. Cheng with the synthesis of analogs and handling of data. M.N.S. and K.Y. thank the Maple Syrup Urine Disease Family Group for inspiration and guidance and K. Strauss and K. Brigatti, Clinic for Special Children, Strasburg, Pennsylvania, for advice on testing and applications of leucine sensors. K.Y. thanks B.-T. Zhang for introducing her to hypernetwork theory, which led to insertion-reselection designs. M.N.S. dedicates the work to his teachers of organic chemistry, Y. Kishi and B. Solaja. The project was supported by the NIH (voriconazole, leucine, other small molecules, and general conceptualization of functional group–based approach, GM138843 to M.N.S.; neurotransmitters, DA045550 to A.M.A.; ...

العلاقة: https://doi.org/10.1126/science.abn9859Test; oai:authors.library.caltech.edu:1twdw-maf93; eprintid:122402; resolverid:CaltechAUTHORS:20230725-746162000.27

الإتاحة: https://doi.org/10.1126/science.abn9859Test

المؤلفون: Zimmerman, Zoe E., Cleveland, Rebecca J., Kostic, Aleksandra M., Leifer, Valia P., Weisner, Serena E., Allen, Kelli D., Golightly, Yvonne M., Welch, Heather, Dale, Melissa, Messier, Stephen P., Hunter, David J., Katz, Jeffrey N., Callahan, Leigh F., Losina, Elena

المساهمون: National Institute of Arthritis and Musculoskeletal and Skin Diseases, Centers for Disease Control and Prevention

المصدر: Osteoarthritis and Cartilage Open ; volume 5, issue 3, page 100368 ; ISSN 2665-9131

مصطلحات موضوعية: General Medicine

الإتاحة: https://doi.org/10.1016/j.ocarto.2023.100368Test
https://api.elsevier.com/content/article/PII:S2665913123000353?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2665913123000353?httpAccept=text/plainTest

المؤلفون: Kostic, Aleksandra M., Arbeeva, Liubov, Jiang, Xiaotong, Golightly, Yvonne M., Messier, Stephen P., Loeser, Richard F., Borgert, J.E., De Marchi, Daniel, Marron, JS, Kosorok, Michael R., Nelson, Amanda E.

المصدر: Osteoarthritis and Cartilage ; volume 32, page S65-S66 ; ISSN 1063-4584

مصطلحات موضوعية: Orthopedics and Sports Medicine, Biomedical Engineering, Rheumatology

الإتاحة: https://doi.org/10.1016/j.joca.2024.02.097Test
https://api.elsevier.com/content/article/PII:S1063458424001420?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1063458424001420?httpAccept=text/plainTest

المؤلفون: Kostic, Aleksandra M., Leifer, Valia P., Selzer, Faith, Hunter, David J., Paltiel, A. David, Chen, Antonia F., Robinson, Malcolm K., Neogi, Tuhina, Collins, Jamie E., Messier, Stephen P., Edwards, Robert R., Katz, Jeffrey N., Losina, Elena

المصدر: Arthritis Care & Research; Aug2023, Vol. 75 Issue 8, p1752-1763, 12p

مصطلحات موضوعية: TOTAL knee replacement, WEIGHT loss, COST effectiveness, OBESITY, SLEEVE gastrectomy

مستخلص: Objective: Class III obesity (body mass index >40 kg/m2) is associated with higher complications following total knee replacement (TKR), and weight loss is recommended. We aimed to establish the cost‐effectiveness of Roux‐en‐Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and lifestyle nonsurgical weight loss (LNSWL) interventions in knee osteoarthritis patients with class III obesity considering TKR. Methods: Using the Osteoarthritis Policy model and data from published literature to derive model inputs for RYGB, LSG, LNSWL, and TKR, we assessed the long‐term clinical benefits, costs, and cost‐effectiveness of weight‐loss interventions for patients with class III obesity considering TKR. We assessed the following strategies with a health care sector perspective: 1) no weight loss/no TKR, 2) immediate TKR, 3) LNSWL, 4) LSG, and 5) RYGB. Each weight‐loss strategy was followed by annual TKR reevaluation. Primary outcomes were cost, quality‐adjusted life expectancy (QALE), and incremental cost‐effectiveness ratios (ICERs), discounted at 3% per year. We conducted deterministic and probabilistic sensitivity analyses to examine the robustness of conclusions to input uncertainty. Results: LSG increased QALE by 1.64 quality‐adjusted life‐years (QALYs) and lifetime medical costs by $17,347 compared to no intervention, leading to an ICER of $10,600/QALY. RYGB increased QALE by 0.22 and costs by $4,607 beyond LSG, resulting in an ICER of $20,500/QALY. Relative to immediate TKR, LSG and RYGB delayed and decreased TKR utilization. In the probabilistic sensitivity analysis, RYGB was cost‐effective in 67% of iterations at a willingness‐to‐pay threshold of $50,000/QALY. Conclusion: For patients with class III obesity considering TKR, RYGB provides good value while immediate TKR without weight loss is not economically efficient. [ABSTRACT FROM AUTHOR]

: Copyright of Arthritis Care & Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: MacFarlane, Lindsey A., Arant, Kaetlyn R., Kostic, Aleksandra M., Mass, Hanna, Jones, Morgan H., Collins, Jamie E., Losina, Elena, Katz, Jeffrey N.

المصدر: Arthritis Care & Research; Aug2023, Vol. 75 Issue 8, p1783-1787, 5p

مصطلحات موضوعية: LEUKOCYTE count, SYNOVITIS, SYNOVIAL fluid, KNEE pain, MAGNETIC resonance imaging, KNEE osteoarthritis, INFLAMMATION

مستخلص: Objective: Inflammation is a potential pain generator and treatment target in knee osteoarthritis (OA). Inflammation can be detected on magnetic resonance imaging (MRI) and by synovial fluid white blood cell count (WBC). However, the performance characteristics of synovial fluid WBC for the detection of synovitis have not been established. This study was undertaken to determine the sensitivity and specificity of synovial fluid WBC in identifying inflammation in knee OA using MRI effusion‐synovitis as the gold standard. Methods: We identified records of patients seen at an academic center with a diagnosis code for knee OA, a procedural code for knee aspiration, and a laboratory order for synovial fluid WBC in the same encounter, as well as an MRI within 12 months of the aspiration. MRIs were read for effusion‐synovitis using the MRI OA Knee Score (MOAKS). We dichotomized effusion‐synovitis as 1) none or small, or 2) medium or large. We calculated the sensitivity and specificity of synovial fluid WBC using MRI effusion‐synovitis (medium/large) as the gold standard. We used the Youden index to identify the best cut point. Results: We included 75 patients. Mean ± SD age was 63 ± 12 years, and 69% were female. The synovial fluid WBC was higher in the medium/large effusion‐synovitis group (median 335 [interquartile range (IQR) 312]) than in the none/small group (median 194 [IQR 272]). The optimal cut point was 242, yielding a sensitivity of 71% (95% confidence interval [95% CI] 56–83%) and specificity of 63% (95% CI 41–81%). Conclusion: The sensitivity and specificity of synovial fluid WBC in identifying effusion‐synovitis on MRI were limited. Further research is needed to better understand the association between MRI and effusion‐synovitis measured by synovial fluid and to determine which measure more strongly relates to synovial histopathology and patient outcomes. [ABSTRACT FROM AUTHOR]

: Copyright of Arthritis Care & Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: MacFarlane, Lindsey A., Arant, Kaetlyn R., Kostic, Aleksandra M., Mass, Hanna, Jones, Morgan H., Collins, Jamie E., Losina, Elena, Katz, Jeffrey N.

المصدر: Arthritis Care and Research; August 2023, Vol. 75 Issue: 8 p1783-1787, 5p

مستخلص: Inflammation is a potential pain generator and treatment target in knee osteoarthritis (OA). Inflammation can be detected on magnetic resonance imaging (MRI) and by synovial fluid white blood cell count (WBC). However, the performance characteristics of synovial fluid WBC for the detection of synovitis have not been established. This study was undertaken to determine the sensitivity and specificity of synovial fluid WBC in identifying inflammation in knee OA using MRI effusion‐synovitis as the gold standard. We identified records of patients seen at an academic center with a diagnosis code for knee OA, a procedural code for knee aspiration, and a laboratory order for synovial fluid WBC in the same encounter, as well as an MRI within 12 months of the aspiration. MRIs were read for effusion‐synovitis using the MRI OA Knee Score (MOAKS). We dichotomized effusion‐synovitis as 1) none or small, or 2) medium or large. We calculated the sensitivity and specificity of synovial fluid WBC using MRI effusion‐synovitis (medium/large) as the gold standard. We used the Youden index to identify the best cut point. We included 75 patients. Mean ± SD age was 63 ± 12 years, and 69% were female. The synovial fluid WBC was higher in the medium/large effusion‐synovitis group (median 335 [interquartile range (IQR) 312]) than in the none/small group (median 194 [IQR 272]). The optimal cut point was 242, yielding a sensitivity of 71% (95% confidence interval [95% CI] 56–83%) and specificity of 63% (95% CI 41–81%). The sensitivity and specificity of synovial fluid WBC in identifying effusion‐synovitis on MRI were limited. Further research is needed to better understand the association between MRI and effusion‐synovitis measured by synovial fluid and to determine which measure more strongly relates to synovial histopathology and patient outcomes.

المؤلفون: Yang, Kyungae, Mitchell, Noelle M., Banerjee, Saswata, Zhenzhuang Cheng, Taylor, Steven, Kostic, Aleksandra M., Wong, Isabel, Sajjath, Sairaj, Yameng Zhang, Stevens, Jacob, Mohan, Sumit, Landry, Donald W., Worgall, Tilla S., Andrews, Anne M., Stojanovic, Milan N.

المصدر: Science; 6/2/2023, Vol. 380 Issue 6648, p942-948, 7p, 4 Color Photographs

المؤلفون: Kostic, Aleksandra M., Leifer, Valia P., Gong, Yusi, Robinson, Malcolm K., Collins, Jamie E., Neogi, Tuhina, Messier, Stephen P., Hunter, David J., Selzer, Faith, Suter, Lisa G., Katz, Jeffrey N., Losina, Elena

المصدر: Arthritis Care & Research; Mar2023, Vol. 75 Issue 3, p491-500, 10p

مصطلحات موضوعية: GASTRIC bypass, KNEE osteoarthritis, TOTAL knee replacement, COST effectiveness, SLEEVE gastrectomy, KNEE pain

مستخلص: Objective: Class III obesity (body mass index [BMI] ≥40 kg/m2) is associated with worse knee pain and total knee replacement (TKR) outcomes. Because bariatric surgery yields sustainable weight loss for individuals with BMI ≥40 kg/m2, our objective was to establish the value of Roux‐en‐Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) in conjunction with usual care for knee osteoarthritis (OA) patients with BMI ≥40 kg/m2. Methods: We used the Osteoarthritis Policy model to assess long‐term clinical benefits, costs, and cost‐effectiveness of RYGB and LSG. We derived model inputs for efficacy, costs, and complications associated with these treatments from published data. Primary outcomes included quality‐adjusted life‐years (QALYs), lifetime costs, and incremental cost‐effectiveness ratios (ICERs), all discounted at 3%/year. This analysis was conducted from a health care sector perspective. We performed sensitivity analyses to evaluate uncertainty in input parameters. Results: The usual care + RYGB strategy increased the quality‐adjusted life expectancy by 1.35 years and lifetime costs by $7,209, compared to usual care alone (ICER = $5,300/QALY). The usual care + LSG strategy yielded less benefit than usual care + RYGB and was dominated. Relative to usual care alone, both usual care + RYGB and usual care + LSG reduced opioid use from 13% to 4%, and increased TKR usage from 30% to 50% and 41%, respectively. For cohorts with BMI between 38 and 41 kg/m2, usual care + LSG dominated usual care + RYGB. In the probabilistic sensitivity analysis, at a willingness‐to‐pay threshold of $50,000/QALY, usual care + RYGB and usual care + LSG were cost‐effective in 70% and 30% of iterations, respectively. Conclusion: RYGB offers good value among knee OA patients with BMI ≥40 kg/m2, while LSG may provide good value among those with BMI between 35 and 41 kg/m2. [ABSTRACT FROM AUTHOR]

: Copyright of Arthritis Care & Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Kostic, Aleksandra M., Leifer, Valia P., Gong, Yusi, Robinson, Malcolm K., Collins, Jamie E., Neogi, Tuhina, Messier, Stephen P., Hunter, David J., Selzer, Faith, Suter, Lisa G., Katz, Jeffrey N., Losina, Elena

المساهمون: National Institute of Arthritis and Musculoskeletal and Skin Diseases

المصدر: Arthritis Care & Research ; volume 75, issue 3, page 491-500 ; ISSN 2151-464X 2151-4658

الوصف: Objective Class III obesity (body mass index [BMI] ≥40 kg/m 2 ) is associated with worse knee pain and total knee replacement (TKR) outcomes. Because bariatric surgery yields sustainable weight loss for individuals with BMI ≥40 kg/m 2 , our objective was to establish the value of Roux‐en‐Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) in conjunction with usual care for knee osteoarthritis (OA) patients with BMI ≥40 kg/m 2 . Methods We used the Osteoarthritis Policy model to assess long‐term clinical benefits, costs, and cost‐effectiveness of RYGB and LSG. We derived model inputs for efficacy, costs, and complications associated with these treatments from published data. Primary outcomes included quality‐adjusted life‐years (QALYs), lifetime costs, and incremental cost‐effectiveness ratios (ICERs), all discounted at 3%/year. This analysis was conducted from a health care sector perspective. We performed sensitivity analyses to evaluate uncertainty in input parameters. Results The usual care + RYGB strategy increased the quality‐adjusted life expectancy by 1.35 years and lifetime costs by $7,209, compared to usual care alone (ICER = $5,300/QALY). The usual care + LSG strategy yielded less benefit than usual care + RYGB and was dominated. Relative to usual care alone, both usual care + RYGB and usual care + LSG reduced opioid use from 13% to 4%, and increased TKR usage from 30% to 50% and 41%, respectively. For cohorts with BMI between 38 and 41 kg/m 2 , usual care + LSG dominated usual care + RYGB. In the probabilistic sensitivity analysis, at a willingness‐to‐pay threshold of $50,000/QALY, usual care + RYGB and usual care + LSG were cost‐effective in 70% and 30% of iterations, respectively. Conclusion RYGB offers good value among knee OA patients with BMI ≥40 kg/m 2 , while LSG may provide good value among those with BMI between 35 and 41 kg/m 2 .

الإتاحة: https://doi.org/10.1002/acr.24967Test