436 results on '"Rong Sen Yang"'
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2. Arsenic and diabetes: Current perspectives
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Chun Fa Huang, Ya Wen Chen, Ching Yao Yang, Keh Sung Tsai, Rong Sen Yang, and Shing Hwa Liu
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Arsenic ,Diabetes mellitus ,Epidemiological studies ,Experimental studies ,Medicine (General) ,R5-920 - Abstract
Arsenic is a naturally occurring toxic metalloid of global concern. Many studies have indicated a dose–response relationship between accumulative arsenic exposure and the prevalence of diabetes mellitus (DM) in arseniasis-endemic areas in Taiwan and Bangladesh, where arsenic exposure occurs through drinking water. Epidemiological researches have suggested that the characteristics of arsenic-induced DM observed in arseniasis-endemic areas in Taiwan and Mexico are similar to those of non-insulin-dependent DM (Type 2 DM). These studies analyzed the association between high and chronic exposure to inorganic arsenic in drinking water and the development of DM, but the effect of exposure to low to moderate levels of inorganic arsenic on the risk of DM is unclear. Navas-Acien et al. recently proposed that a positive association existed between total urine arsenic and the prevalence of Type 2 DM in people exposed to low to moderate levels of arsenic. However, the diabetogenic role played by arsenic is still debated upon. An increase in the prevalence of DM has been observed among residents of highly arsenic-contaminated areas, whereas the findings from community-based and occupational studies in low-arsenic-exposure areas have been inconsistent. Recently, a population-based cross-sectional study showed that the current findings did not support an association between arsenic exposure from drinking water at levels less than 300 μg/L and a significantly increased risk of DM. Moreover, although the precise mechanisms for the arsenic-induced diabetogenic effect are still largely undefined, recent in vitro experimental studies indicated that inorganic arsenic or its metabolites impair insulin-dependent glucose uptake or glucose-stimulated insulin secretion. Nevertheless, the dose, the form of arsenic used, and the experimental duration in the in vivo studies varied greatly, leading to conflicting results and ambiguous interpretation of these data with respect to human exposure to arsenic in the environment. Moreover, the experimental studies were limited to the use of arsenic concentrations much higher than those relevant to human exposure. Further prospective epidemiological studies might help to clarify this controversy. The issues about environmental exposure assessment and appropriate biomarkers should also be considered. Here, we focus on the review of mechanism studies and discuss the currently available evidence and conditions for the association between environmental arsenic exposure and the development of DM.
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- 2011
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3. Advanced glycation end products induce peroxisome proliferator-activated receptor γ down-regulation-related inflammatory signals in human chondrocytes via Toll-like receptor-4 and receptor for advanced glycation end products.
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Ying Ju Chen, Meei Ling Sheu, Keh Sung Tsai, Rong Sen Yang, and Shing Hwa Liu
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Medicine ,Science - Abstract
Accumulation of advanced glycation end products (AGEs) in joints is important in the development of cartilage destruction and damage in age-related osteoarthritis (OA). The aim of this study was to investigate the roles of peroxisome proliferator-activated receptor γ (PPARγ), toll-like receptor 4 (TLR4), and receptor for AGEs (RAGE) in AGEs-induced inflammatory signalings in human OA chondrocytes. Human articular chondrocytes were isolated and cultured. The productions of metalloproteinase-13 and interleukin-6 were quantified using the specific ELISA kits. The expressions of related signaling proteins were determined by Western blotting. Our results showed that AGEs enhanced the productions of interleukin-6 and metalloproteinase-13 and the expressions of cyclooxygenase-2 and high-mobility group protein B1 and resulted in the reduction of collagen II expression in human OA chondrocytes. AGEs could also activate nuclear factor (NF)-κB activation. Stimulation of human OA chondrocytes with AGEs significantly induced the up-regulation of TLR4 and RAGE expressions and the down-regulation of PPARγ expression in a time- and concentration-dependent manner. Neutralizing antibodies of TLR4 and RAGE effectively reversed the AGEs-induced inflammatory signalings and PPARγ down-regulation. PPARγ agonist pioglitazone could also reverse the AGEs-increased inflammatory signalings. Specific inhibitors for p38 mitogen-activated protein kinases, c-Jun N-terminal kinase and NF-κB suppressed AGEs-induced PPARγ down-regulation and reduction of collagen II expression. Taken together, these findings suggest that AGEs induce PPARγ down-regulation-mediated inflammatory signalings and reduction of collagen II expression in human OA chondrocytes via TLR4 and RAGE, which may play a crucial role in the development of osteoarthritis pathogenesis induced by AGEs accumulation.
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- 2013
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4. Urban–rural differences in outcomes and management of vertebral fractures: A real-world observational study
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Chirn-Bin Chang, Rong-Sen Yang, Wei-Jia Huang, Yi-Chun Chou, Chiung-Jung Wen, Ting-Chun Huang, Ming-Chang Chen, and Ding-Cheng Chan
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Fracture liaison service ,Osteoporosis ,Vertebral fracture ,Urban-rural differences ,Medicine (General) ,R5-920 - Abstract
Background: A fracture liaison services (FLSs) and its modified services reduce refractures and mortality and can be cost-effective. Limited studies have addressed whether urban–rural differences exist in vertebral fracture outcomes and management. Therefore, the aims of the study were to investigate any urban–rural differences in refracture, mortality, prescription pattern, and associated factors of vertebral fractures after receiving assistance from an FLSs. Methods: Baseline characteristics and osteoporosis medication prescription patterns of participants were collected. After 1-year follow-up, mortality, refracture rate, and osteoporosis medication switching and adherence were evaluated. Multivariate logistic regressions were performed to identify baseline correlates on one-year mortality. Results: There was higher mortality rate in the rural group but no urban–rural difference in the 1-year refracture rate after implementation of FLSs and medication management services (MMSs). The types of osteoporosis medications prescribed for both groups were similar, but participants in the rural group were less likely to change their osteoporosis medications during the 1-year follow-up timeframe and with lower adherence rate. The likelihood of being older and having chronic kidney disease, osteoarthritis, and neurological disease was higher in the rural group. Conclusion: Our multicomponent services have similar effectiveness in osteoporosis treatment between urban and rural areas. The overall adherence rate was lower in the rural group with higher mortality but no difference in the refracture rate in one year.
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- 2023
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5. Comparison of eight modern preoperative scoring systems for survival prediction in patients with extremity metastasis
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Tse‐Ying Lee, Yu‐An Chen, Olivier Q. Groot, Hung‐Kuan Yen, Bas J. J. Bindels, Robert‐Jan Pierik, Hsiang‐Chieh Hsieh, Aditya V. Karhade, Ting‐En Tseng, Yi‐Hsiang Lai, Jing‐Jen Yang, Chia‐Che Lee, Ming‐Hsiao Hu, Jorrit‐Jan Verlaan, Joseph H. Schwab, Rong‐Sen Yang, and Wei‐Hsin Lin
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Asian cohort ,external validation ,extremity metastasis ,survival prediction models ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Survival is an important factor to consider when clinicians make treatment decisions for patients with skeletal metastasis. Several preoperative scoring systems (PSSs) have been developed to aid in survival prediction. Although we previously validated the Skeletal Oncology Research Group Machine‐learning Algorithm (SORG‐MLA) in Taiwanese patients of Han Chinese descent, the performance of other existing PSSs remains largely unknown outside their respective development cohorts. We aim to determine which PSS performs best in this unique population and provide a direct comparison between these models. Methods We retrospectively included 356 patients undergoing surgical treatment for extremity metastasis at a tertiary center in Taiwan to validate and compare eight PSSs. Discrimination (c‐index), decision curve (DCA), calibration (ratio of observed:expected survivors), and overall performance (Brier score) analyses were conducted to evaluate these models’ performance in our cohort. Results The discriminatory ability of all PSSs declined in our Taiwanese cohort compared with their Western validations. SORG‐MLA is the only PSS that still demonstrated excellent discrimination (c‐indexes>0.8) in our patients. SORG‐MLA also brought the most net benefit across a wide range of risk probabilities on DCA with its 3‐month and 12‐month survival predictions. Conclusions Clinicians should consider potential ethnogeographic variations of a PSS's performance when applying it onto their specific patient populations. Further international validation studies are needed to ensure that existing PSSs are generalizable and can be integrated into the shared treatment decision‐making process. As cancer treatment keeps advancing, researchers developing a new prediction model or refining an existing one could potentially improve their algorithm's performance by using data gathered from more recent patients that are reflective of the current state of cancer care.
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- 2023
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6. A ubiquitous endocrine disruptor tributyltin induces muscle wasting and retards muscle regeneration
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Hsien‐Chun Chiu, Rong‐Sen Yang, Te‐I Weng, Chen‐Yuan Chiu, Kuo‐Cheng Lan, and Shing‐Hwa Liu
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Tributyltin ,Environmental pollutants ,Muscle regeneration ,Muscle wasting ,Diseases of the musculoskeletal system ,RC925-935 ,Human anatomy ,QM1-695 - Abstract
Abstract Background Organotin pollutant tributyltin (TBT) is an environmental endocrine disrupting chemical and is a known obesogen and diabetogen. TBT can be detected in human following consumption of contaminated seafood or water. The decrease in muscle strength and quality has been shown to be associated with type 2 diabetes in older adults. However, the adverse effects of TBT on the muscle mass and function still remain unclear. Here, we investigated the effects and molecule mechanisms of low‐dose TBT on skeletal muscle regeneration and atrophy/wasting using the cultured skeletal muscle cell and adult mouse models. Methods The mouse myoblasts (C2C12) and differentiated myotubes were used to assess the in vitro effects of low‐dose tributyltin (0.01–0.5 μM). The in vivo effects of TBT at the doses of 5 and 25 μg/kg/day (n = 6/group), which were five times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively, by oral administration for 4 weeks on muscle wasting and muscle regeneration were evaluated in a mouse model with or without glycerol‐induced muscle injury/regeneration. Results TBT reduced myogenic differentiation in myoblasts (myotube with 6–10 nuclei: 53.9 and 35.8% control for 0.05 and 0.1 μM, respectively, n = 4, P 0.05 and P 0.05 and P 0.05 and P
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- 2023
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7. Impact of the Requirement of Bone Mineral Density Evidence on Utilization of Anti-osteoporosis Medications, Clinical Outcome and Medical Expenditures of Patient With Hip Fracture in Taiwan
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Chen-Yu Wang, Shau-Huai Fu, Chih-Chien Hung, Rong-Sen Yang, Jou-Wei Lin, Ho-Min Chen, Fei-Yuan Hsiao, and Li-Jiuan Shen
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osteoporosis ,osteoporotic fracture ,national health insurance ,anti-osteoporosis medications ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundSince 2011, Taiwan’s National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. MethodsBy using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender-specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. ResultsOur study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old. ConclusionThe regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.
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- 2022
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8. Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update
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Ta-Wei Tai, Chun-Feng Huang, Huei-Kai Huang, Rong-Sen Yang, Jung-Fu Chen, Tien-Tsai Cheng, Fang-Ping Chen, Chung-Hwan Chen, Yin-Fan Chang, Wei-Chieh Hung, Der-Sheng Han, Ding-Cheng Chan, Ching-Chou Tsai, I-Wen Chen, Wing P. Chan, Husan-Jui Chang, Jawl-Shan Hwang, and Chih-Hsing Wu
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Anti-osteoporosis treatment ,Fracture liaison service ,Guidelines ,Osteoporosis ,Osteoporotic fracture ,Medicine (General) ,R5-920 - Abstract
Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.
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- 2023
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9. Diagnostic accuracy of algorithms to define incident and second hip fractures: A Taiwan validation study
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Shau-Huai Fu, Ping-Ying Yu, Chung-Yi Li, Chih-Chien Hung, Chia-Che Lee, Hsuan-Yu Chen, Ta-Wei Tai, Jawl-Shan Hwang, Rong-Sen Yang, Hongsen Chiang, Sung-Yen Lin, Chih-Hsing Wu, Ling-Chiao Liao, Chin-Ju Chuang, Chiu-Yi Wu, Cheng-Ying Chang, Ming-Tsung Lee, Chung-Hwan Chen, and Chen-Yu Wang
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Diagnostic accuracy ,Hip fractures ,International classification of diseases ,Periprosthetic fracture ,Validity ,Medicine (General) ,R5-920 - Abstract
Background: Previous epidemiological researchers have used various algorithms to identify a second hip fracture; however, there has been no validation of these algorithms to date. This study aimed to verify existing algorithms for identifying second hip fracture under the International Classification of Diseases diagnostic coding systems. Furthermore, we examined the validity of two newly proposed algorithms that integrated the concept of periprosthetic fractures and laterality of the ICD-10 coding system. Methods: Claims data of patients hospitalized for hip fracture from National Taiwan University Hospitals between 2007 and 2020 were retrieved. Hip fracture was confirmed by 2 orthopaedic surgeons with medical records and imaging data as gold standards. The validity of 9 existing and 2 newly proposed algorithms for identifying second hip fracture was evaluated. Results: The positive predictive value (PPV) range between 84% and 90% in existing algorithms for identifying second hip fractures. Noteworthy, the longer time interval for discrimination resulted in slightly increased PPV (from 87% to 90%), while decreased sensitivity noticeably (from 87% to 72%). When considering the information about periprosthetic fracture, the PPV increased to 91% without diminished sensitivity. The PPV of the newly proposed ICD-10-specific algorithm was 100%. Conclusion: Algorithms integrated clinical insights of periprosthetic fractures and laterality concept of ICD-10 coding system provided satisfactory validity and help precisely define second hip fracture in future database research.
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- 2023
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10. The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations
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Chia-Che Lee, Shau-Huai Fu, Ho-Min Chen, Jou-Wei Lin, Chih-Cheng Hsu, Sheng-Chieh Lin, Jawl-Shan Hwang, Rong-Sen Yang, Chih-Hsing Wu, and Chen-Yu Wang
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Adherence ,Antiosteoporosis medication ,Denosumab ,Medication possession ratio ,Zoledronate ,Medicine (General) ,R5-920 - Abstract
Background: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. Methods: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. Results: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. Conclusion: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.
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- 2023
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11. Asia–pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures
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Chun-Feng Huang, Jung-Fu Chen, Ian R. Reid, Wing P. Chan, Peter Robert Ebeling, Bente Langdahl, Shih-Te Tu, Toshio Matsumoto, Ding-Cheng Chan, Yoon-Sok Chung, Fang-Ping Chen, E Michael Lewiecki, Keh-Sung Tsai, Rong-Sen Yang, Seng Bin Ang, Ko-En Huang, Yin-Fan Chang, Chung-Hwan Chen, Joon-Kiong Lee, Hsin-I Ma, Weibo Xia, Ambrish Mithal, David L. Kendler, Cyrus Cooper, Jawl-Shan Hwang, and Chih-Hsing Wu
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Asia–pacific ,Consensus ,Osteoporosis ,Osteoporotic fracture ,Postmenopausal women ,Prevention ,Medicine (General) ,R5-920 - Abstract
Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia–Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.
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- 2023
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12. Eleven years secular trend of the initiation of anti-osteoporosis medications and subsequent fractures in Taiwan: From 2008 to 2018
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Tsung-Han Yang, Chen-Yu Wang, Shau-Huai Fu, Ding-Cheng Chan, Ho-Min Chen, Jou-Wei Lin, Chun-Feng Huang, Jen-Jia Yang, Chih-Hsing Wu, Jawl-Shan Hwang, and Rong-Sen Yang
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Osteoporosis ,Secular trend ,Anti-Osteoporosis medications ,Subsequent fractures ,Medicine (General) ,R5-920 - Abstract
Background: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. Methods: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients
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- 2023
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13. Osteoporosis care after hip fracture: Observation from national health insurance database and fracture liaison services
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Chun-Feng Huang, Sheng-Chieh Lin, Ho-Min Chen, Chih-Hsing Wu, Shih-Te Tu, Rong-Sen Yang, Wei-Jia Huang, Jawl-Shan Hwang, and Ding-Cheng Chan
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Adherence ,Fracture liaison service ,Hip fracture ,Osteoporosis ,Medicine (General) ,R5-920 - Abstract
Background: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). Methods: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. Results: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. Conclusion: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.
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- 2023
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14. Constraining in reimbursement criteria and the adherence to anti-osteoporosis medications (AOMs) in Taiwan: Urbanization makes the difference
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Chen-Yu Wang, Tsung-Han Yang, Shau-Huai Fu, Jawl-Shan Hwang, Ho-Min Chen, Jou-Wei Lin, Chih-Cheng Hsu, Yin-Fan Chang, Chih-Hsing Wu, Ding-Cheng Chan, and Rong-Sen Yang
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Osteoporosis ,Anti-osteoporosis medications ,Urbanization ,Adherence ,Medicine (General) ,R5-920 - Abstract
Background: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. Methods: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. Results: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (
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- 2023
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15. Bone Cement Implantation Syndrome in Bone Tumor Surgeries: Incidence, Risk Factors, and Clinical Experience
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Tsung‐han Yang, Rong‐sen Yang, Chih‐peng Lin, and Tzu‐hao Tseng
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Arthroplasty ,Bone cement implantation syndrome ,Bone tumor surgery ,Hypotension ,Orthopedic surgery ,RD701-811 - Abstract
Objective To investigate the incidence and risk factors of bone cement implantation syndrome (BCIS) in bone tumor surgeries. Methods This was a retrospective observational study. We investigated patients who underwent bone tumor surgeries requiring cementation as part of the surgery between March 2016 and January 2018. We reviewed medical records, including formal anesthesia records and operation notes. Patients with complete data files were included. To investigate the general incidence of BCIS in tumor surgeries, patients of all ages, genders and tumor types were included. Vital signs, including oxygen saturation, blood pressure, heart rate, and respiratory rate, were checked and recorded once every 1–2 min after cementation. Accurate time points of cementation were recorded on formal anesthesia record sheets by the anesthesiologists. The definition and severity of BCIS were based on the classification system proposed in previous studies: grade I, moderate hypoxia (SpO2 20%); grade II, severe hypoxia (SpO2 40%) or unexpected loss of consciousness; and grade III, cardiovascular collapse requiring cardiopulmonary resuscitation. We also compared the incidence of BCIS between those patients with and without possible risk factors, including intraoperative blood loss, arthroplasty, use of an intramedullary device, patient age, gender, tumor location, and preexisting lung cancer or lung metastasis. Results A total of 88 patients were included. BCIS occurred in 23 patients, with an incidence of 26.1%. Among them, 19 had grade I and 4 had grade II BCIS. There was no patients with grade III BCIS. The lowest blood pressure occurred within 10 min in 21 (87.5%) patients and within 20 min for all patients. A total of 9 grade I BCIS were self‐limiting. The other 10 grade I hypotension cases and all grade II hypotension cases recovered after administration of a vasoconstrictor medication. Preexisting lung cancer or lung metastasis was the risk factor for BCIS; 40.0% of patients (16 in 40 patients) with preexisting lung cancer or metastasis had BCIS, whereas only 14.6% of patients (7 in 48 patients) without lung lesions had BCIS. There was no risk difference in terms of arthroplasty, old age, and increased blood loss. Apart from grades I and II bone cement implantation syndrome, there were no other major complications, including death, cardiovascular events, or cerebrovascular events. Conclusion Bone cement implantation syndrome is not unusual in bone tumor surgeries, and preexisting lung cancer or lung metastasis is a risk factor.
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- 2021
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16. A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial
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Chia-Che Lee, Chen-Yu Wang, Chih-Chien Hung, Chuan-Ching Huang, Chung-Yi Li, Hsuan-Yu Chen, Yun-Liang Chang, Wo-Jan Tseng, Ting-Ming Wang, Rong-Sen Yang, Tze-Hong Wong, and Shau-Huai Fu
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denosumab ,rebound effect ,osteoporosis ,zoledronate ,bone loss ,bone mineral density ,Medicine (General) ,R5-920 - Abstract
Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033.Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life.Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.
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- 2021
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17. Plasticizer Di-(2-ethylhexyl) Phthalate and Its Metabolite Mono(2-ethylhexyl) Phthalate Inhibit Myogenesis in Differentiating Mouse and Human Skeletal Muscle Cell Models
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Kuo-Cheng Lan, Te-I Weng, Wei-Che Chiang, Chen-Yuan Chiu, Ding-Cheng Chan, Rong-Sen Yang, and Shing-Hwa Liu
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plasticizer phthalates ,DEHP ,MEHP ,Akt signaling ,myogenesis ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
The relationship between plasticizer di(2-ethylhexyl) phthalate (DEHP) and low birth weight in neonates has been reported. Immature muscle differentiation may be involved in low birth weight. The myotoxic characteristics of chemicals have been observed in differentiating immortalized and primary muscle cells. Here, we explored the myotoxic effects of DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) in vitro using the immortalized mouse skeletal myoblasts C2C12 and primary human skeletal muscle progenitor cell (HSMPC) models. We found that both DEHP and MEHP at the concentrations of 10–100 μM, which were non- and low-cytotoxicity concentrations, significantly and dose-dependently inhibited the creatine kinase activity, myotube formation with multiple nuclei, and myogenin and myosin heavy chain (muscle differentiation markers) protein expression in C2C12 and HSMPCs under differentiation medium. Both DEHP and MEHP significantly decreased Akt phosphorylation in C2C12 and HSMPCs during differentiation. Taken together, DEHP and its metabolite MEHP are capable of inhibiting Akt-regulated myogenesis in myoblasts/myogenic progenitors during differentiation. These findings suggest the possibility of DEHP as an environmental risk factor affecting skeletal myogenic differentiation. Moreover, these in vitro muscle cell models may be a possible alternative method to animal myotoxicity testing.
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- 2022
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18. Ne-(1-Carboxymethyl)-L-lysine/RAGE Signaling Drives Metastasis and Cancer Stemness through ERK/NFκB axis in Osteosarcoma.
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Ting-Yu Chang, Kuo-Cheng Lan, Chia-Hung Wu, Meei-Ling Sheu, Rong-Sen Yang, and Shing-Hwa Liu
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- 2024
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19. SaFeplay: a lightweight portable sensing system to estimate knee adduction moment.
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Shih-Yao Wei, Yi-Ping Lo, Chia-Yi Lin, Tse-Yu Lin, Yin-Yu Chou, Jung-Tang Huang, Rong-Sen Yang, and Yi-Ping Hung
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- 2017
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20. Application of deep learning algorithm to detect and visualize vertebral fractures on plain frontal radiographs.
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Hsuan-Yu Chen, Benny Wei-Yun Hsu, Yu-Kai Yin, Feng-Huei Lin, Tsung-Han Yang, Rong-Sen Yang, Chih-Kuo Lee, and Vincent S Tseng
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Medicine ,Science - Abstract
BackgroundIdentification of vertebral fractures (VFs) is critical for effective secondary fracture prevention owing to their association with the increasing risks of future fractures. Plain abdominal frontal radiographs (PARs) are a common investigation method performed for a variety of clinical indications and provide an ideal platform for the opportunistic identification of VF. This study uses a deep convolutional neural network (DCNN) to identify the feasibility for the screening, detection, and localization of VFs using PARs.MethodsA DCNN was pretrained using ImageNet and retrained with 1306 images from the PARs database obtained between August 2015 and December 2018. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were evaluated. The visualization algorithm gradient-weighted class activation mapping (Grad-CAM) was used for model interpretation.ResultsOnly 46.6% (204/438) of the VFs were diagnosed in the original PARs reports. The algorithm achieved 73.59% accuracy, 73.81% sensitivity, 73.02% specificity, and an AUC of 0.72 in the VF identification.ConclusionComputer driven solutions integrated with the DCNN have the potential to identify VFs with good accuracy when used opportunistically on PARs taken for a variety of clinical purposes. The proposed model can help clinicians become more efficient and economical in the current clinical pathway of fragile fracture treatment.
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- 2021
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21. Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis
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Chih-Hsing Wu, Wei-Chieh Hung, Ing-Lin Chang, Tsung-Ting Tsai, Yin-Fan Chang, Eugene V. McCloskey, Nelson B. Watts, Michael R. McClung, Chun-Feng Huang, Chung-Hwan Chen, Kun-Ling Wu, Keh-Sung Tsai, Ding-Cheng Chan, Jung-Fu Chen, Shih-Te Tu, Jawl-Shan Hwang, Weibo Xia, Toshio Matsumoto, Yoon-Sok Chung, Cyrus Cooper, John A. Kanis, Rong-Sen Yang, and Wing P. Chan
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Fracture ,Low bone mass ,Osteopenia ,Osteoporosis ,Primary prevention ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Objectives: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results: Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. Conclusion: The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.
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- 2020
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22. Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging
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Yao-Pang Chung, Te-I Weng, Ding-Cheng Chan, Rong-Sen Yang, and Shing-Hwa Liu
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Health, Toxicology and Mutagenesis ,General Medicine ,Toxicology - Abstract
Tributyltin (TBT) is known as an endocrine-disrupting chemical. This study investigated the effects and possible mechanisms of TBT exposure on inducing human articular chondrocyte senescence in vitro at the human-relevant concentrations of 0.01-0.5 μM and mouse articular cartilage aging in vivo at the doses of 5 and 25 μg/kg/day, which were 5 times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively. TBT significantly increased the senescence-associated β-galactosidase activity and the protein expression levels of senescence markers p16, p53, and p21 in chondrocytes. TBT induced the protein phosphorylation of both p38 and JNK mitogen-activated protein kinases in which the JNK signaling was a main pathway to be involved in TBT-induced chondrocyte senescence. The phosphorylation of both ataxia-telangiectasia mutated (ATM) and histone protein H2AX (termed γH2AX) was also significantly increased in TBT-treated chondrocytes. ATM inhibitor significantly inhibited the protein expression levels of γH2AX, phosphorylated p38, phosphorylated JNK, p16, p53, and p21. TBT significantly stimulated the mRNA expression of senescence-associated secretory phenotype (SASP)-related factors, including IL-1β, TGF-β, TNF-α, ICAM-1, CCL2, and MMP13, and the protein expression of GATA4 and phosphorylated NF-κB-p65 in chondrocytes. Furthermore, TBT by oral gavage for 4 weeks in mice significantly enhanced the articular cartilage aging and abrasion. The protein expression of phosphorylated p38, phosphorylated JNK, GATA4, and phosphorylated NF-κB-p65, and the mRNA expression of SASP-related factors were enhanced in the mouse cartilages. These results suggest that TBT exposure can trigger human chondrocyte senescence in vitro and accelerating mouse articular cartilage aging in vivo.
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- 2022
23. Prognostic significance of lab data and performance comparison by validating survival prediction models for patients with spinal metastases after radiotherapy
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Hung-Kuan Yen, Ming-Hsiao Hu, Hester Zijlstra, Olivier Q. Groot, Hsiang-Chieh Hsieh, Jiun-Jen Yang, Aditya V. Karhade, Po-Chao Chen, Yu-Han Chen, Po-Hao Huang, Yu-Hung Chen, Fu-Ren Xiao, Jorrit-Jan Verlaan, Joseph H. Schwab, Rong-Sen Yang, Shu-Hua Yang, Wei-Hsin Lin, and Feng-Ming Hsu
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Spinal Neoplasms ,Oncology ,Albumins ,Humans ,Radiology, Nuclear Medicine and imaging ,Hematology ,Prognosis ,Alkaline Phosphatase ,Aged ,Retrospective Studies - Abstract
Well-performing survival prediction models (SPMs) help patients and healthcare professionals to choose treatment aligning with prognosis. This retrospective study aims to investigate the prognostic impacts of laboratory data and to compare the performances of Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy (METSSS) model, New England Spinal Metastasis Score (NESMS), and Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) for spinal metastases (SM).From 2010 to 2018, patients who received radiotherapy (RT) for SM at a tertiary center were enrolled and the data were retrospectively collected. Multivariate logistic and Cox-proportional-hazard regression analyses were used to assess the association between laboratory values and survival. The area under receiver-operating characteristics curve (AUROC), calibration analysis, Brier score, and decision curve analysis were used to evaluate the performance of SPMs.A total of 2786 patients were included for analysis. The 90-day and 1-year survival rates after RT were 70.4% and 35.7%, respectively. Higher albumin, hemoglobin, or lymphocyte count were associated with better survival, while higher alkaline phosphatase, white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or international normalized ratio were associated with poor prognosis. SORG-MLA has the best discrimination (AUROC 90-day, 0.78; 1-year 0.76), best calibrations, and the lowest Brier score (90-day 0.16; 1-year 0.18). The decision curve of SORG-MLA is above the other two competing models with threshold probabilities from 0.1 to 0.8.Laboratory data are of prognostic significance in survival prediction after RT for SM. Machine learning-based model SORG-MLA outperforms statistical regression-based model METSSS model and NESMS in survival predictions.
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- 2022
24. Can a Bayesian belief network for survival prediction in patients with extremity metastases (PATHFx) be externally validated in an Asian cohort of 356 surgically treated patients?
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Hsiang-Chieh Hsieh, Yi-Hsiang Lai, Chia-Che Lee, Hung-Kuan Yen, Ting-En Tseng, Jiun-Jen Yang, Shin-Yiing Ling, Ming-Hsiao Hu, Chun-Han Hou, Rong-Sen Yang, Rikard Wedin, Jonathan A Forsberg, and Wei-Hsin Lin
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Cohort Studies ,Humans ,Bayes Theorem ,Bone Neoplasms ,Extremities ,Orthopedics and Sports Medicine ,Surgery ,General Medicine ,Prognosis ,Decision Support Techniques - Abstract
Background and purpose: Predicted survival may influence the treatment decision for patients with skeletal extremity metastasis, and PATHFx was designed to predict the likelihood of a patient dying in the next 24 months. However, the performance of prediction models could have ethnogeographical variations. We asked if PATHFx generalized well to our Taiwanese cohort consisting of 356 surgically treated patients with extremity metastasis.Patients and methods: We included 356 patients who underwent surgery for skeletal extremity metastasis in a tertiary center in Taiwan between 2014 and 2019 to validate PATHFx’s survival predictions at 6 different time points. Model performance was assessed by concordance index (c-index), calibration analysis, decision curve analysis (DCA), Brier score, and model consistency (MC).Results: The c-indexes for the 1-, 3-, 6-, 12-, 18-, and 24-month survival estimations were 0.71, 0.66, 0.65, 0.69, 0.68, and 0.67, respectively. The calibration analysis demonstrated positive calibration intercepts for survival predictions at all 6 timepoints, indicating PATHFx tended to underestimate the actual survival. The Brier scores for the 6 models were all less than their respective null model’s. DCA demonstrated that only the 6-, 12-, 18-, and 24-month predictions appeared useful for clinical decision-making across a wide range of threshold probabilities. The MC was < 0.9 when the 6- and 12-month models were compared with the 12-month and 18-month models, respectively.Interpretation: In this Asian cohort, PATHFx’s performance was not as encouraging as those of prior validation studies. Clinicians should be cognizant of the potential decline in validity of any tools designed using data outside their particular patient population. Developers of survival prediction tools such as PATHFx might refine their algorithms using data from diverse, contemporary patients that is more reflective of the world’s population.
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- 2022
25. Real-world cost-effectiveness analysis of the fracture liaison services model of care for hip fracture in Taiwan
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Tsung Han Yang, Ding-Cheng Chan, Yi Fan Li, Wei Jia Huang, Li Nien Chien, Rong-Sen Yang, Yi Han Chen, Hsin Yi Tsai, and Chun Yi Li
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musculoskeletal diseases ,Medicine (General) ,medicine.medical_specialty ,Cost-Benefit Analysis ,Taiwan ,Pharmacy ,Hip fracture ,Cohort Studies ,03 medical and health sciences ,R5-920 ,0302 clinical medicine ,Humans ,Medicine ,Net monetary benefit ,skin and connective tissue diseases ,Hip Fractures ,business.industry ,Cost-effectiveness analysis ,General Medicine ,University hospital ,medicine.disease ,Confidence interval ,030220 oncology & carcinogenesis ,Propensity score matching ,Economic evaluation ,Physical therapy ,030211 gastroenterology & hepatology ,business ,Fracture liaison service (FLS) ,Cohort study - Abstract
Background This study was to perform an economic evaluation to understand clinical outcomes and health resource use between hip fracture patients receiving hospital-based postfracture fracture liaison service (FLS) care and those receiving usual care (UC) in Taiwan. Methods This cohort study included hospital-based data of 174 hip fracture patients who received FLS care (FLS group) from National Taiwan University Hospital, and 1697 propensity score-matched patients who received UC (UC group) of National Health Insurance claim-based data. Two groups had similar baseline characteristics but differed in hip fracture care after propensity score matching. Clinical outcomes included refracture-free survival (RFS), hip-refracture-free survival (HRFS), and overall survival (OS). Health resource use included inpatient, outpatient, and pharmacy costs within 2 years follow-up after the index of hip fracture. The economic evaluation of the FLS model was analyzed using the net monetary benefit regression framework based on the National Health Insurance perspective. Results The FLS group had longer RFS than the UC group, with an adjusted difference of 44.3 days (95% confidence interval: 7.2–81.4 days). Two groups did not differ in inpatient and outpatient costs during follow-up, but the FLS group had a higher expenditure than the UC group on osteoporosis-related medication. The probability of FLS being cost-effective was >80% and of increasing RFS, HRFS, and OS was 95%, 81%, and 80%, respectively, when the willingness-to-pay threshold was >USD 65/gross domestic product per day. Conclusion FLS care was cost-effective in reducing refracture occurrence days for patients initially diagnosed with hip fractures.
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- 2022
26. Urban–rural differences in outcomes and management of vertebral fractures: A real-world observational study
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Chirn-Bin Chang, Rong-Sen Yang, Wei-Jia Huang, Yi-Chun Chou, Chiung-Jung Wen, Ting-Chun Huang, Ming-Chang Chen, and Ding-Cheng Chan
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General Medicine - Abstract
A fracture liaison services (FLSs) and its modified services reduce refractures and mortality and can be cost-effective. Limited studies have addressed whether urban-rural differences exist in vertebral fracture outcomes and management. Therefore, the aims of the study were to investigate any urban-rural differences in refracture, mortality, prescription pattern, and associated factors of vertebral fractures after receiving assistance from an FLSs.Baseline characteristics and osteoporosis medication prescription patterns of participants were collected. After 1-year follow-up, mortality, refracture rate, and osteoporosis medication switching and adherence were evaluated. Multivariate logistic regressions were performed to identify baseline correlates on one-year mortality.There was higher mortality rate in the rural group but no urban-rural difference in the 1-year refracture rate after implementation of FLSs and medication management services (MMSs). The types of osteoporosis medications prescribed for both groups were similar, but participants in the rural group were less likely to change their osteoporosis medications during the 1-year follow-up timeframe and with lower adherence rate. The likelihood of being older and having chronic kidney disease, osteoarthritis, and neurological disease was higher in the rural group.Our multicomponent services have similar effectiveness in osteoporosis treatment between urban and rural areas. The overall adherence rate was lower in the rural group with higher mortality but no difference in the refracture rate in one year.
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- 2022
27. International Validation of the SORG Machine-learning Algorithm for Predicting the Survival of Patients with Extremity Metastases Undergoing Surgical Treatment
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Yi-Hsiang Lai, Jorrit-Jan Verlaan, Wei-Hsin Lin, Olivier Q. Groot, Jia-Chi Ko, Jing-Jen Yang, Hung-Kuan Yen, Rong-Sen Yang, Aditya V. Karhade, Chia-Che Lee, Ting-En Tseng, Joseph H. Schwab, Chun-Han Hou, Shin-Ying Lin, Ming-Hsiao Hu, and Michiel E.R. Bongers
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Adult ,Male ,Calibration (statistics) ,Taiwan ,Bone Neoplasms ,Logistic regression ,Machine Learning ,Breast cancer ,Predictive Value of Tests ,Clinical Research ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Postoperative Period ,Aged ,Aged, 80 and over ,Performance status ,business.industry ,Extremities ,General Medicine ,Odds ratio ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Brier score ,Cohort ,Female ,Surgery ,business ,Algorithm - Abstract
BACKGROUND The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data. QUESTIONS/PURPOSES (1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions? METHODS All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% [116 of 356]) and breast cancer (16% [58 of 356]). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% [210 of 356]), followed by plate screw fixation (23% [81 of 356]) and endoprosthetic reconstruction (18% [65 of 356]). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index [c-index]), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study. RESULTS The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 [95% CI 0.46 to 1.10], calibration slope 0.74 [95% CI 0.53 to 0.96]; 1-year survival prediction: calibration intercept 0.75 [95% CI 0.49 to 1.00], calibration slope 1.22 [95% CI 0.95 to 1.49]). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 [95% CI 1.01 to 3.73]) but not 1-year mortality (OR 1.07 [95% CI 0.53 to 2.17]) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively. CONCLUSION SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE Level III, therapeutic study.
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- 2021
28. Increased fracture risk after discontinuation of anti‐osteoporosis medications among hip fracture patients: A population‐based cohort study
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Shau Huai Fu, C.‐Y. Li, Fei-Yuan Hsiao, Rong-Sen Yang, Chui Jia Farn, Wei-Hsin Lin, Chih Chien Hung, Jou-Wei Lin, Chen-Yu Wang, Chuan Ching Huang, Ho Min Chen, and Chia Che Lee
- Subjects
education.field_of_study ,Hip fracture ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,Osteoporosis ,Population ,Hazard ratio ,medicine.disease ,Discontinuation ,Denosumab ,Internal medicine ,Internal Medicine ,medicine ,education ,business ,medicine.drug ,Cohort study - Abstract
Background To compare the risks of major osteoporotic, vertebral, and non-vertebral fractures between patients who discontinued anti-osteoporosis medications. Methods We conducted a comparative effectiveness study with a nationwide population-based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least one year were included. Patients were categorized into persistent or non-persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non-vertebral fracture. Multivariate, time-varying Cox proportional hazards model was used to evaluate the risk of major outcomes. Results Compared with persistent denosumab users, non-persistent denosumab users had a significantly higher risk of major osteoporotic fractures (Hazard ratio (HR) = 1.60; 95% confidence interval (CI), 1.20 to 2.14),vertebral fractures (HR = 2.18; 95% CI, 1.46 to 3.24) and death (HR = 3.57; 95%CI, 2.63-4.84). However, the increased risk of fracture was not found in both persistent and non-persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non-persistent denosumab users was more pronounced within one-year post discontinuation (HR = 2.90, 95% CI, 1.77 to 4.74) and among patients who discontinued from 2-year denosumab therapy (HR = 3.58; 95% CI, 1.74 to7.40). Discussion Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within one-year post discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture. This article is protected by copyright. All rights reserved.
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- 2021
29. A ubiquitous endocrine disruptor tributyltin induces muscle wasting and retards muscle regeneration
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Hsien‐Chun Chiu, Rong‐Sen Yang, Te‐I Weng, Chen‐Yuan Chiu, Kuo‐Cheng Lan, and Shing‐Hwa Liu
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Physiology (medical) ,Orthopedics and Sports Medicine - Abstract
Organotin pollutant tributyltin (TBT) is an environmental endocrine disrupting chemical and is a known obesogen and diabetogen. TBT can be detected in human following consumption of contaminated seafood or water. The decrease in muscle strength and quality has been shown to be associated with type 2 diabetes in older adults. However, the adverse effects of TBT on the muscle mass and function still remain unclear. Here, we investigated the effects and molecule mechanisms of low-dose TBT on skeletal muscle regeneration and atrophy/wasting using the cultured skeletal muscle cell and adult mouse models.The mouse myoblasts (C2C12) and differentiated myotubes were used to assess the in vitro effects of low-dose tributyltin (0.01-0.5 μM). The in vivo effects of TBT at the doses of 5 and 25 μg/kg/day (n = 6/group), which were five times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively, by oral administration for 4 weeks on muscle wasting and muscle regeneration were evaluated in a mouse model with or without glycerol-induced muscle injury/regeneration.TBT reduced myogenic differentiation in myoblasts (myotube with 6-10 nuclei: 53.9 and 35.8% control for 0.05 and 0.1 μM, respectively, n = 4, P 0.05). TBT also decreased myotube diameter, upregulated protein expression levels of muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1), myostatin, phosphorylated AMPKα, and phosphorylated NFκB-p65, and downregulated protein expression levels of phosphorylated AKT and phosphorylated FoxO1 in myotubes (0.2 and 0.5 μM, n = 6, P 0.05). Exposure of TBT in mice elevated body weight, decreased muscle mass, and induced muscular dysfunction (5 and 25 μg/kg, P 0.05 and P 0.05, respectively, n = 6). TBT inhibited soleus muscle regeneration in mice with glycerol-induced muscle injury (5 and 25 μg/kg, P 0.05 and P 0.05, respectively, n = 6). TBT upregulated protein expression levels of Atrogin-1, MuRF1, myostatin, and phosphorylated AMPKα and downregulated protein expression level of phosphorylated FoxO1 in the mouse soleus muscles (5 and 25 μg/kg, P 0.05 and P 0.05, respectively, n = 6).This study demonstrates for the first time that low-dose TBT significantly inhibits myogenic differentiation and triggers myotube atrophy in a cell model and significantly decreases muscle regeneration and muscle mass and function in a mouse model. These findings suggest that low-dose TBT exposure may be an environmental risk factor for muscle regeneration inhibition, atrophy/wasting, and disease-related myopathy.
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- 2022
30. The Effects of Zoledronic Acid Treatment and Endurance Exercise on Ovariectomy-induced Osteopenia in Wistar Rats
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Hsin-Shih Lin, Rong-Sen Yang, Jack L. Lewis, Ming-shi Chang, Ar-Tyan Hsu, and Tsang-Hai Huang
- Abstract
Background: This study investigated the effects of endurance exercise training and zoledronic acid (Zol) treatment on ovariectomy-induced osteopenia. Methods: Middle-aged female Wistar rats were subjected to sham and ovariectomy surgeries and assigned to seven different groups according to Zol treatment doses and treadmill endurance exercise training; these were the Sham, Ovx, LowZ, HighZ, EXE, LowZ+EXE, HighZ+EXE groups. The subcutaneous (s.c.) doses of Zol for the LowZ and HighZ groups were 20 and 100 µg/kg, respectively. Total intervention period was 10 weeks. Results: Both Zol treatment and exercise training significantly blunted ovariectomy-induced osteopenia in spongy bone (pConclusions: Though exercise training did not demonstrate significantly synergistic or modifying effects to Zol-treated bone, results from energy, aging and bone related serum measurements indicate that exercise might reveal its benefits in later phases or at lower doses of bisphosphonate.
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- 2022
31. CORR Insights®: Do Liquid Nitrogen-treated Tumor-bearing Nerve Grafts Have the Capacity to Regenerate, and Do They Pose a Risk of Local Recurrence? A Study in Rats
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Rong-Sen Yang
- Subjects
Nitrogen ,Neoplasms ,Animals ,Orthopedics and Sports Medicine ,Surgery ,General Medicine ,Neurosurgical Procedures ,Rats - Published
- 2022
32. One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system
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Chirn-Bin Chang, Keh-Sung Tsai, Jen-Kuei Peng, Rong-Sen Yang, Ding-Cheng Chan, Lo-Yu Chang, Tsung Han Yang, and Wei-Jia Huang
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0301 basic medicine ,Secondary prevention ,medicine.medical_specialty ,Hip fracture ,business.industry ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,030209 endocrinology & metabolism ,medicine.disease ,Rheumatology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Orthopedic surgery ,Cohort ,medicine ,Vitamin D and neurology ,030101 anatomy & morphology ,business ,Healthcare system - Abstract
Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.
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- 2021
33. Bone Cement Implantation Syndrome in Bone Tumor Surgeries: Incidence, Risk Factors, and Clinical Experience
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Tzu‐hao Tseng, Tsung‐han Yang, Chih‐peng Lin, and Rong-Sen Yang
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Bone cement implantation syndrome ,Bone Neoplasms ,Metastasis ,Arthroplasty ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,lcsh:Orthopedic surgery ,Risk Factors ,medicine ,Humans ,Orthopedics and Sports Medicine ,Lung cancer ,Aged ,Retrospective Studies ,030222 orthopedics ,Clinical Article ,Lung ,business.industry ,Incidence ,Medical record ,Bone Cements ,Retrospective cohort study ,Syndrome ,Middle Aged ,Bone cement ,medicine.disease ,Surgery ,lcsh:RD701-811 ,Blood pressure ,medicine.anatomical_structure ,Bone tumor surgery ,Clinical Articles ,Female ,Hypotension ,business ,030217 neurology & neurosurgery - Abstract
Objective To investigate the incidence and risk factors of bone cement implantation syndrome (BCIS) in bone tumor surgeries. Methods This was a retrospective observational study. We investigated patients who underwent bone tumor surgeries requiring cementation as part of the surgery between March 2016 and January 2018. We reviewed medical records, including formal anesthesia records and operation notes. Patients with complete data files were included. To investigate the general incidence of BCIS in tumor surgeries, patients of all ages, genders and tumor types were included. Vital signs, including oxygen saturation, blood pressure, heart rate, and respiratory rate, were checked and recorded once every 1–2 min after cementation. Accurate time points of cementation were recorded on formal anesthesia record sheets by the anesthesiologists. The definition and severity of BCIS were based on the classification system proposed in previous studies: grade I, moderate hypoxia (SpO2 20%); grade II, severe hypoxia (SpO2 40%) or unexpected loss of consciousness; and grade III, cardiovascular collapse requiring cardiopulmonary resuscitation. We also compared the incidence of BCIS between those patients with and without possible risk factors, including intraoperative blood loss, arthroplasty, use of an intramedullary device, patient age, gender, tumor location, and preexisting lung cancer or lung metastasis. Results A total of 88 patients were included. BCIS occurred in 23 patients, with an incidence of 26.1%. Among them, 19 had grade I and 4 had grade II BCIS. There was no patients with grade III BCIS. The lowest blood pressure occurred within 10 min in 21 (87.5%) patients and within 20 min for all patients. A total of 9 grade I BCIS were self‐limiting. The other 10 grade I hypotension cases and all grade II hypotension cases recovered after administration of a vasoconstrictor medication. Preexisting lung cancer or lung metastasis was the risk factor for BCIS; 40.0% of patients (16 in 40 patients) with preexisting lung cancer or metastasis had BCIS, whereas only 14.6% of patients (7 in 48 patients) without lung lesions had BCIS. There was no risk difference in terms of arthroplasty, old age, and increased blood loss. Apart from grades I and II bone cement implantation syndrome, there were no other major complications, including death, cardiovascular events, or cerebrovascular events. Conclusion Bone cement implantation syndrome is not unusual in bone tumor surgeries, and preexisting lung cancer or lung metastasis is a risk factor., The incidence of bone cement implantation syndrome (BCIS) in bone tumor surgeries was 26%. The incidence of grade I and grade II BCIS was 22% and 4%, respectively.
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- 2021
34. Relationship Between Body Composition and Balance Performance in Older Adults with Hyperkyphosis
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Rong-Sen Yang, Pei-Yu Su, Chien-Wen Hou, Shiow-Chwen Tsai, Phunsuk Kantha, and Wei-Li Hsu
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medicine.medical_specialty ,business.industry ,0206 medical engineering ,Biomedical Engineering ,02 engineering and technology ,General Medicine ,Stride length ,Muscle mass ,020601 biomedical engineering ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Balance performance ,Inclination angle ,Medicine ,Bone mineral content ,Decreased muscle mass ,business ,Heel strike ,Balance (ability) - Abstract
Older adults with hyperkyphosis might have a high risk of falls since their whole body center of mass may shift to the boundary of the base of support. Body composition changes, such as low bone mineral content (BMC), decreased muscle mass, high body mass index (BMI), and increased fat mass are common in older adults with hyperkyphosis. This study aimed to investigate the relationship between body composition and balance performance using a biomechanical analysis in older adults with hyperkyphosis. Thirty older adults with hyperkyphosis were recruited. BMC, muscle mass, BMI, and fat mass were measured for body composition. Balance performances were determined with walking, quiet standing, and forward reach. Gait speed, step length, center of mass–center of pressure inclination angle of heel strike (Inc-HS) and toe off (Inc-TO) during walking, center of mass–center of pressure inclination angle during quiet standing (Inc-QS), and reaching distance were calculated. BMC had a moderately positive correlation with gait speed (r = 0.48, p
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- 2020
35. CARMA3 Promotes Colorectal Cancer Cell Motility and Cancer Stemness via YAP-Mediated NF-κB Activation
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Meei-Ling Sheu, Ting-Yu Chang, Rong-Sen Yang, Shing-Hwa Liu, and Cheng-Tien Wu
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Cancer Research ,Gene knockdown ,cancer stem cell ,biology ,Slug ,Cell growth ,Colorectal cancer ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,colorectal cancer ,medicine.disease ,biology.organism_classification ,Article ,NF-κB ,Metastasis ,CARMA3 ,YAP ,metastasis ,Oncology ,Tumor progression ,Cancer stem cell ,medicine ,Cancer research ,RC254-282 - Abstract
Simple Summary CARMA3 is overexpressed in most cancers, and its expression is positively associated with poor prognosis. In this study, we evaluated the detailed mechanisms of CARMA3-mediated CRC metastasis. We found that overexpression of CARMA3 induced the expression of YAP and NF-κB activation, then elicited EMT induction to enhance cell migration and invasion. We demonstrate for the first time that YAP is a critical downstream regulator of CARMA3 in CRC. Our findings reveal a regulation axis between CARMA3 and Hippo oncoprotein YAP and further support the potential role of CARMA3 in the metastasis and cancer stemness of CRC. Abstract CARD-recruited membrane-associated protein 3 (CARMA3) is overexpressed in various cancers and is associated with cancer cell proliferation, metastasis, and tumor progression; however, the underlying mechanisms of CARMA3 in colorectal cancer (CRC) metastasis remain unclear. Here, we found that higher CARMA3 expression was correlated with poor overall survival and metastasis in CRC patients from the TNMplot database and Human Tissue Microarray staining. Elevating CARMA3 expression promoted cell proliferation, epithelial-mesenchymal transition (EMT) induction, migration/invasion abilities, sphere formation, and cancer stem cell markers expression. Knockdown of CARMA3 decreased these processes via the EMT-related transcription factor Slug. Moreover, CARMA3 depletion significantly reduced tumor growth in mice that were consistent with the in vitro results. CRC migration/invasion could be regulated by CARMA3/YAP/Slug signaling axis using genetic inhibition of Yes-associated protein (YAP). Interestingly, CARMA3 induced activation of nuclear factor (NF)-κB through YAP expression, contributing to upregulation of Slug. YAP expression positively correlated with CARMA3, NF-κB, and Slug gene expression and poor clinical outcomes in CRC patients. Our findings demonstrate for the first time that CARMA3 plays an important role in CRC progression, which may serve as a potential diagnostic biomarker and candidate therapeutic target for CRC treatment.
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- 2021
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36. Developing a clinical scoring system to differentiate deep-seated atypical lipomatous tumor from lipoma of soft tissue
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Hao-Chih Tai, Rong-Sen Yang, Bo-Ching Lee, Yin Cheng, An-Ta Ko, Jou-Hsuan Huang, Cher-Wei Liang, and Nai-Chen Cheng
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Adult ,Male ,Surgical margin ,medicine.medical_specialty ,Scoring system ,lcsh:Surgery ,Soft Tissue Neoplasms ,Malignancy ,Sensitivity and Specificity ,Atypical Lipomatous Tumor ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Tumor biopsy ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Soft tissue ,Magnetic resonance imaging ,Liposarcoma ,lcsh:RD1-811 ,Middle Aged ,Lipoma ,medicine.disease ,Magnetic Resonance Imaging ,Research Design ,030220 oncology & carcinogenesis ,Preoperative Period ,Female ,030211 gastroenterology & hepatology ,Surgery ,Radiology ,business - Abstract
Summary: Background: Atypical lipomatous tumor (ALT) is a low-grade malignancy that frequently occurs at a subfascial anatomical location. While marginal excision is adequate for lipomas, excision with a surgical margin is suggested for ALTs. However, ALTs and lipomas are difficult to differentiate preoperatively, even with the help of imaging studies. In this study, we aimed to formulate a scoring system based on selected clinical and imaging characteristics to enhance the accuracy of pre-operative diagnosis of deep-seated ALTs. Methods: We enrolled 417 cases of deep-seated lipoma and 53 cases of ALTs from soft tissue treated between 2005 and 2016. Tumors arising from the bone, internal cavities, retroperitoneum, or nervous system were excluded. Clinical data were analyzed along with magnetic resonance image (MRI) features. We further developed a scoring formula to distinguish deep-seated ALTs from lipomas. Results: Older age, tumor location at lower limbs, and the presence of MRI features (larger size, thick septa > 2 mm, contrast enhancement>1 cm, fat component
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- 2019
37. Fracture types affect clinical outcomes of patients managed within the fracture liaison and osteoporosis medication management services
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Lo-Yu Chang, Tsung Han Yang, Ding-Cheng Chan, Keh-Sung Tsai, Jen-Kuei Peng, Chirn-Bin Chang, Wei-Jia Huang, and Rong-Sen Yang
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Male ,Risk ,0301 basic medicine ,Aging ,medicine.medical_specialty ,Osteoporosis ,lcsh:Medicine ,Osteoarthritis ,Logistic regression ,Article ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Bone Density ,Risk Factors ,Internal medicine ,medicine ,Humans ,lcsh:Science ,Aged ,Hip fracture ,Fracture repair ,Multidisciplinary ,Bone Density Conservation Agents ,Hip Fractures ,business.industry ,Mortality rate ,Malnutrition ,lcsh:R ,Secondary data ,medicine.disease ,030104 developmental biology ,Geriatrics ,Spinal Fractures ,Accidental Falls ,Female ,lcsh:Q ,business ,Body mass index ,Osteoporotic Fractures ,030217 neurology & neurosurgery ,Kidney disease - Abstract
Osteoporosis medication in fragility fracture patients is associated with better outcomes. However, limited studies have investigated whether fracture types affect outcomes among patients undergoing treatment. We performed a secondary data analysis on participants from a fracture liaison service and an osteoporosis medication management service. Participants (n = 974) were regrouped into hip fracture (HF), vertebral fracture (VF), HF + VF, and NO HF/VF groups at baseline. Bivariate and multivariate logistic regressions were performed to identify baseline correlates on one-year mortality, incident refractures, and falls. Baseline characteristics were different among fracture groups. The HF group was oldest, with the lowest body mass index (BMI), lowest FRAX® T-score and had the highest 10-year fracture risk. After intervention, the HF group still had the highest mortality, but the HF + VF group had the highest refracture and incident fall rates. In the multivariate regression analysis, prevalent HF and VF, lower BMI and albumin level, and having chronic kidney disease or cancer were associated with higher mortality rates. HF + VF patients had the highest refracture risk. Prevalent HF and VF, older age and higher BMI, and having cancer or osteoarthritis were associated with a greater fall risk. HF and VF are associated with adverse outcomes, even under an optimal fracture care.
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- 2019
38. Use of dipeptidyl peptidase‐4 inhibitors and the risk of arthralgia: Population‐based cohort and nested case–control studies
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Rong-Sen Yang, Shau-Huai Fu, Fei-Yuan Hsiao, and Chen-Yu Wang
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Male ,medicine.medical_specialty ,Time Factors ,Databases, Factual ,Epidemiology ,Taiwan ,Risk Assessment ,030226 pharmacology & pharmacy ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Hypoglycemic Agents ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,Proportional Hazards Models ,Acarbose ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Hazard ratio ,Middle Aged ,Pharmacoepidemiology ,Arthralgia ,Confidence interval ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Cohort ,Nested case-control study ,Female ,Thiazolidinediones ,business ,medicine.drug ,Cohort study - Abstract
Purpose The objective of this study was to investigate the association between the administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (cumulative duration, timing, and individual substance) and the risk of arthralgia by using a nationwide database with two methodological approaches including cohort and nested case-control study designs. Methods Using Taiwan's National Health Insurance Research Database, we identified patients who were newly prescribed with DPP-4 inhibitors, thiazolidinediones (TZDs), or acarbose between 1 March 2009 and 31 December 2012. The exposure of studied drugs was categorized into five exclusive categories: DPP-4 inhibitor, TZD, acarbose, combined use, or non-use, and assessed in a time-varying manner. Time-dependent Cox proportional hazard models were used to estimate the association between DPP-4 inhibitors and the risk of arthralgia. Particularly, we tested the impact of different cumulative duration, timing, and individual substance of DPP-4 inhibitors use on risk of arthralgia. A corresponding nested case-control study using conditional logistic regression was conducted to verify this association. Results An increased risk of arthralgia was observed during the first year after initiating DPP-4 inhibitors (adjusted Hazard Ratio = 1.35; 95% confidence interval [CI], 1.04-1.75) but the risk declined with cumulative use. This duration-response relation was not found in TZDs use and acarbose use. In the nested case-control study, there was a slightly increased risk of arthralgia (aOR = 1.08; 95% CI, 1.04-1.12) associated with current DPP-4 inhibitor use. Conclusion A relatively higher risk of arthralgia was associated with the initial administration of DPP-4 inhibitors, however, the risk declined among long-term users.
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- 2019
39. The Implications of Osteoporosis in Orthopedic Surgery
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Rong-Sen Yang
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medicine.medical_specialty ,business.industry ,General surgery ,Orthopedic surgery ,Osteoporosis ,medicine ,medicine.disease ,business - Published
- 2021
40. Advances in delivery of health care for MSK conditions
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Michael Hurley, Ding-Cheng Chan, Kristina Åkesson, Rong-Sen Yang, Anthony D. Woolf, Søren Overgaard, Håkan Nero, Rachelle Buchbinder, Margareta Nordin, Leif Dahlberg, and Lo-Yu Chang
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medicine.medical_specialty ,Orthopaedic surgery ,alliedhealth ,Rheumatology ,Surveys and Questionnaires ,Health care ,medicine ,Back pain ,Humans ,Musculoskeletal Diseases ,Delivery of care ,business.industry ,Joint diseases ,Health services research ,health ,Spine ,Fracture ,Musculoskeletal ,Orthopedic surgery ,High value care ,Physical therapy ,e-health ,medicine.symptom ,business ,Delivery of Health Care - Published
- 2020
41. Application of deep learning algorithm to detect and visualize vertebral fractures on plain frontal radiographs
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Vincent S. Tseng, Chih Kuo Lee, Benny Wei Yun Hsu, Rong-Sen Yang, Yu Kai Yin, Feng-Huei Lin, Hsuan-Yu Chen, and Tsung-Han Yang
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Databases, Factual ,Computer science ,Epidemiology ,Radiography ,Health Care Providers ,02 engineering and technology ,Machine Learning ,0202 electrical engineering, electronic engineering, information engineering ,Medicine and Health Sciences ,Medical Personnel ,Connective Tissue Diseases ,Musculoskeletal System ,Multidisciplinary ,Professions ,Medicine ,Spinal Fractures ,020201 artificial intelligence & image processing ,Fracture prevention ,Anatomy ,Algorithm ,Algorithms ,Research Article ,Computer and Information Sciences ,Neural Networks ,Imaging Techniques ,Science ,Pain ,Research and Analysis Methods ,Sensitivity and Specificity ,Deep Learning ,Signs and Symptoms ,Rheumatology ,Artificial Intelligence ,020204 information systems ,Physicians ,Image Interpretation, Computer-Assisted ,Humans ,Skeleton ,business.industry ,Deep learning ,Biology and Life Sciences ,Fracture treatment ,Spine ,Health Care ,Medical Risk Factors ,People and Places ,Osteoporosis ,Population Groupings ,Artificial intelligence ,Neural Networks, Computer ,Clinical Medicine ,business ,Neuroscience - Abstract
Background Identification of vertebral fractures (VFs) is critical for effective secondary fracture prevention owing to their association with the increasing risks of future fractures. Plain abdominal frontal radiographs (PARs) are a common investigation method performed for a variety of clinical indications and provide an ideal platform for the opportunistic identification of VF. This study uses a deep convolutional neural network (DCNN) to identify the feasibility for the screening, detection, and localization of VFs using PARs. Methods A DCNN was pretrained using ImageNet and retrained with 1306 images from the PARs database obtained between August 2015 and December 2018. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were evaluated. The visualization algorithm gradient-weighted class activation mapping (Grad-CAM) was used for model interpretation. Results Only 46.6% (204/438) of the VFs were diagnosed in the original PARs reports. The algorithm achieved 73.59% accuracy, 73.81% sensitivity, 73.02% specificity, and an AUC of 0.72 in the VF identification. Conclusion Computer driven solutions integrated with the DCNN have the potential to identify VFs with good accuracy when used opportunistically on PARs taken for a variety of clinical purposes. The proposed model can help clinicians become more efficient and economical in the current clinical pathway of fragile fracture treatment.
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- 2020
42. Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis
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Ding-Cheng Chan, Rong-Sen Yang, Michael R. McClung, Weibo Xia, Keh-Sung Tsai, Shih Te Tu, Kun Ling Wu, Jung Fu Chen, Jawl Shan Hwang, Tsung Ting Tsai, Wei Chieh Hung, Toshio Matsumoto, Wing P. Chan, Chung-Hwan Chen, Chun Feng Huang, Nelson B. Watts, John A. Kanis, Eugene V. McCloskey, Yoon Sok Chung, Yin Fan Chang, Ing Lin Chang, Cyrus Cooper, and Chih Hsing Wu
- Subjects
0301 basic medicine ,musculoskeletal diseases ,medicine.medical_specialty ,Low bone mass ,lcsh:Diseases of the musculoskeletal system ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,030209 endocrinology & metabolism ,Placebo ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,Orthopedics and Sports Medicine ,Raloxifene ,Bone mineral ,Primary prevention ,business.industry ,Osteopenia ,Incidence (epidemiology) ,medicine.disease ,Fracture ,Meta-analysis ,030101 anatomy & morphology ,lcsh:RC925-935 ,business ,medicine.drug - Abstract
Objectives Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. Conclusion The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis., Highlights • Bisphosphonates reduced the risk of vertebral fracture in postmenopausal women with osteopenia or osteoporosis but without fracture. • Bisphosphonates increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Limited studies for non-bisphosphonate drugs showed increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Raloxifene decreased the risk of clinical vertebral fractures in postmenopausal women with osteopenia or osteoporosis but without fracture.
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- 2020
43. Impact of the Requirement of Bone Mineral Density Evidence on Utilization of Anti-osteoporosis Medications, Clinical Outcome and Medical Expenditures of Patient With Hip Fracture in Taiwan
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Fei-Yuan Hsiao, Ho-Min Chen, Shau-Huai Fu, Li-Jiuan Shen, Chen-Yu Wang, Chih-Chien Hung, Rong-Sen Yang, and Jou-Wei Lin
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Pediatrics ,medicine.medical_specialty ,Health (social science) ,Leadership and Management ,Osteoporosis ,Population ,Taiwan ,030209 endocrinology & metabolism ,Management, Monitoring, Policy and Law ,03 medical and health sciences ,0302 clinical medicine ,Health Information Management ,Bone Density ,Medicine ,Humans ,030212 general & internal medicine ,Medical prescription ,education ,Reimbursement ,Aged ,Bone mineral ,Aged, 80 and over ,Hip fracture ,education.field_of_study ,business.industry ,Hip Fractures ,Health Policy ,Middle Aged ,medicine.disease ,National health insurance ,Cohort ,Female ,Health Expenditures ,business - Abstract
Background: Since 2011, Taiwan’s National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. Methods: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. Results: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old. Conclusion: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.
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- 2020
44. Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass
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Ding-Cheng Chan, Ching-Chia Wang, Shing-Hwa Liu, Chen-Yuan Chiu, Rong-Sen Yang, and Huang-Jen Chen
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Glycerol ,Male ,0301 basic medicine ,lcsh:Diseases of the musculoskeletal system ,Muscle Development ,Myoblasts ,chemistry.chemical_compound ,0302 clinical medicine ,Muscle regeneration ,Myosin ,Medicine ,Myocyte ,Orthopedics and Sports Medicine ,Acrolein ,Creatine Kinase ,Mice, Inbred ICR ,Myogenesis ,Cell Differentiation ,lcsh:Human anatomy ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Muscle Fatigue ,Original Article ,Environmental Pollutants ,medicine.symptom ,Myoblast ,medicine.medical_specialty ,Cell Survival ,lcsh:QM1-695 ,Cell Line ,03 medical and health sciences ,Muscular Diseases ,Physiology (medical) ,Internal medicine ,Animals ,Regeneration ,Muscle, Skeletal ,Myopathy ,Myogenin ,Soleus muscle ,business.industry ,Akt signalling ,Skeletal muscle ,Original Articles ,030104 developmental biology ,Endocrinology ,chemistry ,lcsh:RC925-935 ,business ,Proto-Oncogene Proteins c-akt - Abstract
Background Acrolein is an extremely electrophilic aldehyde. Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy in vitro. The in vitro and in vivo effects and mechanisms of acrolein on myogenesis and the in vivo effect of acrolein on muscle wasting still remain unclear. Methods C2C12 myoblasts were used to assess the effects of low‐dose acrolein (0.125–1 μM) on myogenesis in vitro. Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5 mg/kg) for 4 weeks with or without glycerol‐induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration. Results Non‐cytotoxic‐concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1 μM, 66.25% and 46.25% control, respectively, n = 4, P
- Published
- 2018
45. Exposure of low-concentration arsenic induces myotube atrophy by inhibiting an Akt signaling pathway
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Chen-Yuan Chiu, Shing-Hwa Liu, Rong-Sen Yang, Kuo-Cheng Lan, and Min-Ni Chung
- Subjects
inorganic chemicals ,0301 basic medicine ,Cell signaling ,medicine.medical_specialty ,Muscle Fibers, Skeletal ,FOXO1 ,Antineoplastic Agents ,AMP-Activated Protein Kinases ,Toxicology ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Atrophy ,Arsenic Trioxide ,Internal medicine ,medicine ,Animals ,Arsenic trioxide ,Phosphorylation ,Protein kinase B ,Akt/PKB signaling pathway ,Myogenesis ,General Medicine ,medicine.disease ,Muscular Atrophy ,030104 developmental biology ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Arsenic, a widely distributed toxic metalloid, has been found to be associated with the low-birth-weight infants and the impairment of muscle regenerative capacity in areas with high levels of arsenic in drinking water. The distal muscular atrophy is one of side effects of arsenic trioxide (As2O3) for acute promyelocytic leukemia therapy. We hypothesized that arsenic may be a potential risk factor for skeletal muscle atrophy. Here, we investigated the action and molecular mechanism of low-dose arsenic on the induction of skeletal muscle atrophy in a skeletal muscle cell model. The differentiated C2C12 myotubes were treated with As2O3 (0.25–1 μM) for 48 h without apparent effects on cell viability. The signaling molecules for myotube atrophy were assessed. Submicromolar-concentration As2O3 dose-dependently triggered C2C12 myotube atrophy and increased the protein expressions of atrogenes Atrogin1 and MuRF1 and inhibited the upstream phosphorylated proteins Akt and FoxO1, while As2O3 dose-dependently increased AMPK phosphorylation in myotubes. Akt activator SC79 could significantly reverse the As2O3-induced myotube atrophy. These results suggest that arsenic is capable of inducing myotube atrophy by inhibiting an Akt signaling pathway.
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- 2019
46. Effects of exercise improves muscle strength and fat mass in patients with high fracture risk: A randomized control trial
- Author
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Ding-Cheng Chan, Cian-Hui Hong, Rong-Sen Yang, Jawl-Shan Hwang, Der-Sheng Han, Keh-Sung Tsai, and Chirn-Bin Chang
- Subjects
Male ,Sarcopenia ,medicine.medical_specialty ,Taiwan ,030209 endocrinology & metabolism ,High fracture ,Risk Assessment ,law.invention ,Fat mass ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Randomized controlled trial ,Bone Density ,law ,medicine ,Humans ,In patient ,Muscle Strength ,030212 general & internal medicine ,Adiposity ,Aged ,Aged, 80 and over ,lcsh:R5-920 ,Hip fracture ,Hip Fractures ,business.industry ,Resistance Training ,Organ Size ,General Medicine ,Middle Aged ,medicine.disease ,Cohort ,Muscle strength ,Physical therapy ,Osteoporosis ,Accidental Falls ,Female ,lcsh:Medicine (General) ,business ,Osteoporotic Fractures - Abstract
Background: The deterioration of the musculoskeletal system imposes significant impact on physical activity. Exercise is an important strategy which minimizes these changes. It is not clear which type of exercise provides better improvement on low physical performance, low muscle mass and low strength of sarcopenia. We aim to develop an integrated care (IC) model and compare its relative efficacy in limb fat free mass, muscle strength, and physical performance with low extremities exercise (LEE) in community dwelling older adults with high risk of fractures (Fracture Risk Assessment Tool (FRAX®)) ≧3% for hip fracture, ≧20% for major osteoporotic fracture or 1-min osteoporosis risk test (≧1 point) or fall (≧2 falls in previous year). Methods: Patients were assigned randomized to participate in either IC or LEE group (n = 55 each) for 3 months. All participants received education including home-based exercise. The IC group consisted of different modalities of exercise while the LEE group performed machine-based low extremities exercise. Fat free mass, muscle strength, and physical performance were measured at their baseline and 3-months follow-up. Results: Mean age was 73.8 ± 7 years with 69.1% women. Entire cohort demonstrated significant increment in fat free mass, muscle strength (4 indicators) and physical performance (3 indicators). However, between group differences were not significant. Conclusion: With regular supervise exercise; both groups are equally effective in decreasing fat mass and increasing physical performance, muscle mass and strength. However, the IC group required fewer resources and thus more financially feasible in a community setting. Keywords: Bone mineral density, Gender differences, Integrated care, Low extremities exercise, Muscle strength
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- 2018
47. The development of Taiwan Fracture Liaison Service network
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Shih-Te Tu, Jen-Kuei Peng, Rong-Sen Yang, Min-Hong Hsieh, Hsusan-Chih Liu, Chin-Hsueh Lin, Chung-Hwan Chen, Wei-Chieh Hung, Yih-Lan Gau, Chi-Chien Niu, Keh-Sung Tsai, Ding-Cheng Chan, Jui-Teng Chien, Lo-Yu Chang, Gau-Tyan Lin, I-Chieh Mao, and Chih Hsing Wu
- Subjects
musculoskeletal diseases ,Population ageing ,lcsh:Diseases of the musculoskeletal system ,media_common.quotation_subject ,Best practice ,education ,Taiwan ,030209 endocrinology & metabolism ,Review Article ,Fracture Liaison Service ,03 medical and health sciences ,0302 clinical medicine ,Promotion (rank) ,Nursing ,Medicine ,Quality (business) ,030212 general & internal medicine ,Accreditation ,media_common ,business.industry ,University hospital ,Best Practice Framework ,Service (economics) ,Osteoporosis ,Fracture prevention ,lcsh:RC925-935 ,business ,Asia-Pacific region - Abstract
Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients. Keywords: Asia-Pacific region, Taiwan, Fracture Liaison Service, Best Practice Framework, Osteoporosis
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- 2018
48. Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation
- Author
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Hsien‐Chun Chiu, Chen‐Yuan Chiu, Rong‐Sen Yang, Ding‐Cheng Chan, Shing‐Hwa Liu, and Chih‐Kang Chiang
- Subjects
lcsh:Diseases of the musculoskeletal system ,Alendronate ,Dysfunction ,Skeletal muscle ,Sirtuin3 ,lcsh:Human anatomy ,Atrophy ,lcsh:RC925-935 ,lcsh:QM1-695 - Abstract
Background A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women. Osteopenic menopausal women with 6 months of alendronate therapy have been observed to improve not only lumbar bone mineral density but also handgrip strength. However, the effect and mechanism of alendronate on muscle strength still remain unclear. Here, we investigated the therapeutic potential and the molecular mechanism of alendronate on the loss of muscle mass and strength in vitro and in vivo. Methods Mouse myoblasts and primary human skeletal muscle‐derived progenitor cells were used to assess the effects of low‐dose alendronate (0.1–1 μM) combined with or without dexamethasone on myotube hypertrophy and myogenic differentiation. Moreover, we also evaluated the effects of low‐dose alendronate (0.5 and 1 mg/kg) by oral administration on the limb muscle function and morphology of mice with denervation‐induced muscle atrophy and glycerol‐induced muscle injury. Results Alendronate inhibited dexamethasone‐induced myotube atrophy and myogenic differentiation inhibition in mouse myoblasts and primary human skeletal muscle‐derived progenitor cells. Alendronate significantly abrogated dexamethasone‐up‐regulated sirtuin‐3 (SIRT3), but not SIRT1, protein expression in myotubes. Both SIRT3 inhibitor AKG7 and SIRT3‐siRNA transfection could also reverse dexamethasone‐up‐regulated atrogin‐1 and SIRT3 protein expressions. Animal studies showed that low‐dose alendronate by oral administration ameliorated the muscular malfunction in mouse models of denervation‐induced muscle atrophy and glycerol‐induced muscle injury with a negative regulation of SIRT3 expression. Conclusions The putative mechanism by which muscle atrophy was improved with alendronate might be through the SIRT3 down‐regulation. These findings suggest that alendronate can be a promising therapeutic strategy for management of muscle wasting‐related diseases and sarcopenia.
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- 2018
49. Preventing muscle wasting by osteoporosis drug alendronatein vitroand in myopathy models via sirtuin-3 down-regulation
- Author
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Chen-Yuan Chiu, Chih-Kang Chiang, Hsien-Chun Chiu, Shing-Hwa Liu, Ding-Cheng Chan, and Rong-Sen Yang
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,Skeletal muscle ,medicine.disease ,Muscle atrophy ,Muscle hypertrophy ,Cachexia ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Atrophy ,Physiology (medical) ,Internal medicine ,Sarcopenia ,Medicine ,Myocyte ,Orthopedics and Sports Medicine ,medicine.symptom ,business ,Myopathy - Abstract
Background A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women. Osteopenic menopausal women with 6 months of alendronate therapy have been observed to improve not only lumbar bone mineral density but also handgrip strength. However, the effect and mechanism of alendronate on muscle strength still remain unclear. Here, we investigated the therapeutic potential and the molecular mechanism of alendronate on the loss of muscle mass and strength in vitro and in vivo. Methods Mouse myoblasts and primary human skeletal muscle-derived progenitor cells were used to assess the effects of low-dose alendronate (0.1-1 μM) combined with or without dexamethasone on myotube hypertrophy and myogenic differentiation. Moreover, we also evaluated the effects of low-dose alendronate (0.5 and 1 mg/kg) by oral administration on the limb muscle function and morphology of mice with denervation-induced muscle atrophy and glycerol-induced muscle injury. Results Alendronate inhibited dexamethasone-induced myotube atrophy and myogenic differentiation inhibition in mouse myoblasts and primary human skeletal muscle-derived progenitor cells. Alendronate significantly abrogated dexamethasone-up-regulated sirtuin-3 (SIRT3), but not SIRT1, protein expression in myotubes. Both SIRT3 inhibitor AKG7 and SIRT3-siRNA transfection could also reverse dexamethasone-up-regulated atrogin-1 and SIRT3 protein expressions. Animal studies showed that low-dose alendronate by oral administration ameliorated the muscular malfunction in mouse models of denervation-induced muscle atrophy and glycerol-induced muscle injury with a negative regulation of SIRT3 expression. Conclusions The putative mechanism by which muscle atrophy was improved with alendronate might be through the SIRT3 down-regulation. These findings suggest that alendronate can be a promising therapeutic strategy for management of muscle wasting-related diseases and sarcopenia.
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- 2018
50. Economic impact and cost-effectiveness of fracture liaison services: a systematic review of the literature
- Author
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M. Achra, H.-C. Liu, T.-T. Cheng, S. Bagga, W.-C. Hung, S.-C. Lin, M.-H. Hsieh, Rong-Sen Yang, I.-J. Kao, and Chih Hsing Wu
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Cost effectiveness ,Cost-Benefit Analysis ,Endocrinology, Diabetes and Metabolism ,Best practice ,MEDLINE ,Psychological intervention ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,Secondary Prevention ,medicine ,Humans ,030212 general & internal medicine ,Economic impact analysis ,health care economics and organizations ,Hip fracture ,business.industry ,Health Care Costs ,Grey literature ,medicine.disease ,Family medicine ,Usual care ,Osteoporosis ,business ,Delivery of Health Care ,Osteoporotic Fractures - Abstract
Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023-$28,800 US dollars (USD) in Japan to $14,513-$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.
- Published
- 2018
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