312 results on '"Hsu, Ma"'
Search Results
202. Title Page
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Hsu, Madeline Y. and Lai, Him Mark
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- 2010
203. Virtual Orientalism: Asian Religions and American Popular Culture (review)
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Hsu, Madeline Y.
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- 2010
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204. Protein, amino acid, and caloric intakes of selected pregnant women
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Wilbur Highley, Elizabeth Hsu Ma, Judith Lewis, Dorothy Woullard, Shanaz Kirmani, Carol S. Williams, Bernadine Tolbert, and Ronald A. Chung
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Adult ,Calorie ,Adolescent ,Anemia ,Physiology ,Blood Pressure ,Pre-Eclampsia ,Glycosuria ,Pregnancy ,Edema ,Medicine ,Humans ,chemistry.chemical_classification ,Nutrition and Dietetics ,Proteinuria ,business.industry ,Nutritional Requirements ,Caloric theory ,Protein amino acid ,medicine.disease ,Amino acid ,Diet ,chemistry ,Female ,Amino Acids, Essential ,Dietary Proteins ,medicine.symptom ,business ,Energy Intake ,Food Science - Abstract
Toxemia of pregnancy is characterized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In three successive trials over three consecutive years, the dietary intakes of a selected number of young pregnant women attending a Maternal and Infant Care Clinic at Tuskegee Institute were evaluated for protein, amino acids, and total calories. Women with toxemia were identified, and women without toxemia served as controls. The toxemic group generally consumed more protein than the controls, but values were statistically significant only in the first trial. However, all essential amino acids were consumed in significantly greater amounts by the toxemic group. Protein and essential amino acids were consumed in adequate amounts (at least two-thirds of the RDA) by both groups but in amounts smaller than the national average. Non-essential amino acids were also consumed in adequate amounts, with the toxemic group consuming larger quantities than the controls. Caloric intakes were adequate for young pregnant women. The relationships of glucosuria and of toxemia to protein and amino acid intake were similar and were opposite to the relationship of anemia to protein and amino acid intake. Meats and grains contributed the greatest quantity of protein and amino acids to the diet in all groups. Data seem to imply that any relationship of protein and amino acids with toxemia of pregnancy is a complex one involving several possibly interrelated nutritional parameters.
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- 1981
205. Decellularized porcine coronary artery with adipose stem cells for vascular tissue engineering.
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Chih-Hsun Lin, Kai Hsia, Chi-Han Tsai, Hsu Ma, Jen-Her Lu, and Ruey-Yug Tsay
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- 2019
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206. The immunomodulator decoy receptor 3 improves locomotor functional recovery after spinal cord injury
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Shie-Liang Hsieh, Hsu Ma, May Jywan Tsai, Wen Hung Huang, Shao Ji Lin, Chuan Wen Chiu, and Henrich Cheng
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Immunology ,Spinal cord injury ,Rats, Sprague-Dawley ,03 medical and health sciences ,Myelin ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine ,Animals ,Humans ,Alternatively activated macrophage ,Cells, Cultured ,Spinal Cord Injuries ,business.industry ,General Neuroscience ,Research ,Receptors, Tumor Necrosis Factor, Member 6b ,Interleukin ,Recovery of Function ,medicine.disease ,M2 Macrophage ,Spinal cord ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Immunohistochemistry ,Female ,Decoy receptor 3 ,DcR3 ,business ,030217 neurology & neurosurgery ,Locomotion - Abstract
Background Spinal cord injury (SCI) causes loss of neurons and axons and results in motor and sensory function impairments. SCI elicits an inflammatory response and induces the infiltration of immune cells, predominantly macrophages, to the injured site. Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member (TNFRSF)-6B, is a pleiotropic immunomodulator capable of inducing macrophage differentiation into the M2 phenotype and enhancing angiogenesis. Because M2 macrophages are crucial for the recovery of impaired motor functions, we ask whether DcR3 is beneficial for the functional recovery of locomotion in Sprague-Dawley (SD) rats after SCI. Methods Contusion injury of the spinal cord was performed using a New York University impactor at the ninth thoracic vertebrae, followed by intrathecal injection of 15 μg recombinant protein comprising DcR3 (DcR3.Fc) in 5 μl of normal saline as the treatment, or 5 μl of normal saline as the control, into the injury epicenter. Functional recovery was evaluated using an open-field test weekly up to 6 weeks after injury. The cavity size and myelin sparing in the rostral-to-caudal region, including the epicenter of the injury, were then examined in SCI rats by histological staining. The expression of anti-inflammatory cytokines and the presence of M2 macrophages were determined by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry at 7 day after SCI. Statistical analysis was performed using a two-tailed Student’s t test. Results Intrathecal administration of DcR3.Fc significantly improved locomotor function and reduced secondary injury with a smaller wound cavity and increased myelin sparing at the lesion site. Compared with the control group, DcR3.Fc-treated rats had increased vascularization at the injury epicenter along with higher levels of interleukin (IL)-4 and IL-10 and lower level of IL-1β on DcR3.Fc-treated rats at day 7 after SCI. Moreover, higher levels of arginase I (Arg I) and CD206 (M2 macrophage markers) and RECA-1 (endothelial marker) were observed in the epicenter on day 7 after SCI by immunofluorescence staining. Conclusions These results indicated that DcR3.Fc may promote the M2 macrophage infiltration and enhanced angiogenesis at the lesion site, thus preserving a greater amount of spinal cord tissues and enhancing functional recovery after SCI.
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207. Chinese American Literature since the 1850s (review)
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Hsu, Madeline Yuan-yin
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- 2002
208. Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer.
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Chih-Ching Yeh, Ming-Feng Hou, Shih-Meng Tsai, Shu-Kai Lin, Jen-Kuei Hsiao, Jung-Chih Huang, Li-Hsuan Wang, Szu-Hsien Wu, Hou, Linda Ann, Hsu Ma, and Li-Yu Tsai
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GLUTATHIONE , *CANCER patients , *SUPEROXIDES , *BREAST cancer - Abstract
Background Reactive oxygen species (ROS), including superoxide anion radical (O2·−), plays an important role in carcinogenesis. The human body has developed different antioxidant systems to defend against free radical attacks. We investigated the changes of the antioxidant status in the blood of patients with breast cancer. Methods The O2·− generation and the levels of malondialdehyde (MDA) were measured as an index of lipid peroxidation along with the examination of the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), the levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and vitamins A, C, and E. Results The results showed that the levels of O2·− and MDA, and the activities of antioxidant enzymes in the blood of the patients with breast cancer were significantly higher than the controls. However, the levels of vitamin C, GSH, GSSG and ratio of GSH/GSSG in the blood of the patients with breast cancer were significantly decreased compared to control subjects. Conclusions Oxidative stress may be involved in breast cancer. The increased activities of erythrocyte antioxidant enzymes may be a compensatory upregulation in response to the increased oxidative stress. [Copyright &y& Elsevier]
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- 2005
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209. TBK1 and IKKε protect target cells from IFNγ-mediated T cell killing via an inflammatory apoptotic mechanism.
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Sun ND, Carr AR, Krogman EN, Chawla Y, Zhong J, Guttormson MC, Chan M, Hsu MA, Dong H, Bogunovic D, Pandey A, Rogers LM, and Ting AT
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Cytotoxic T cells produce interferon gamma (IFNγ), which plays a critical role in anti-microbial and anti-tumor responses. However, it is not clear whether T cell-derived IFNγ directly kills infected and tumor target cells, and how this may be regulated. Here, we report that target cell expression of the kinases TBK1 and IKKε regulate IFNγ cytotoxicity by suppressing the ability of T cell-derived IFNγ to kill target cells. In tumor targets lacking TBK1 and IKKε, IFNγ induces expression of TNFR1 and the Z-nucleic acid sensor, ZBP1, to trigger RIPK1-dependent apoptosis, largely in a target cell-autonomous manner. Unexpectedly, IFNγ, which is not known to signal to NFκB, induces hyperactivation of NFκB in TBK1 and IKKε double-deficient cells. TBK1 and IKKε suppress IKKα/β activity and in their absence, IFNγ induces elevated NFκB-dependent expression of inflammatory chemokines and cytokines. Apoptosis is thought to be non-inflammatory, but our observations demonstrate that IFNγ can induce an inflammatory form of apoptosis, and this is suppressed by TBK1 and IKKε. The two kinases provide a critical connection between innate and adaptive immunological responses by regulating three key responses: (1) phosphorylation of IRF3/7 to induce type I IFN; (2) inhibition of RIPK1-dependent death; and (3) inhibition of NFκB-dependent inflammation. We propose that these kinases evolved these functions such that their inhibition by pathogens attempting to block type I IFN expression would enable IFNγ to trigger apoptosis accompanied by an alternative inflammatory response. Our findings show that loss of TBK1 and IKKε in target cells sensitizes them to inflammatory apoptosis induced by T cell-derived IFNγ., Competing Interests: Conflict of Interest We declare that there are no financial conflicts of interest.
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- 2024
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210. Chinese American Transnational Politics
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LAI, HIM MARK, HSU, MADELINE Y., Edited and with an Introduction by, LAI, HIM MARK, and HSU, MADELINE Y.
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- 2023
211. Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8 + T cells via ME1 up-regulation.
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Gicobi JK, Mao Z, DeFranco G, Hirdler JB, Li Y, Vianzon VV, Dellacecca ER, Hsu MA, Barham W, Yan Y, Mansfield AS, Lin Y, Wu X, Hitosugi T, Owen D, Grams MP, Orme JJ, Lucien F, Zeng H, Park SS, and Dong H
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- Humans, CD8-Positive T-Lymphocytes, Up-Regulation, Salvage Therapy, Neoplasms drug therapy, Antineoplastic Agents
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Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8
+ T cells. We have termed the rebound of cytotoxic CD8+ T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience. Resilient T cells are enriched for CX3CR1+ CD8+ T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8+ T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers. Thus, preserved resilient T cells in patients rebound after salvage therapy and ME1 enhances their resiliency.- Published
- 2023
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212. A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma.
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An Z, Hsu MA, Gicobi JK, Xu T, Harrington SM, Zhang H, Pavelko KD, Hirdler JB, Lohse CM, Nabavizadeh R, Pessoa RR, Sharma V, Thompson RH, Leibovich BC, Dong H, and Lucien F
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- Humans, Immune Checkpoint Inhibitors therapeutic use, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Leukocytes, Mononuclear, T-Lymphocytes, Regulatory, Nephrectomy, CD8-Positive T-Lymphocytes, Carcinoma, Renal Cell drug therapy, Antineoplastic Agents pharmacology, Kidney Neoplasms drug therapy
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The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma., (Copyright © 2023 by The American Association of Immunologists, Inc.)
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- 2023
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213. A Nation of Immigrants Reconsidered : US Society in an Age of Restriction, 1924-1965
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MARINARI, MADDALENA, HSU, MADELINE Y., GARCÍA, MARÍA CRISTINA, MARINARI, MADDALENA, HSU, MADELINE Y., and GARCÍA, MARÍA CRISTINA
- Published
- 2018
214. Cancer-targeted photoimmunotherapy induces antitumor immunity and can be augmented by anti-PD-1 therapy for durable anticancer responses in an immunologically active murine tumor model.
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Hsu MA, Okamura SM, De Magalhaes Filho CD, Bergeron DM, Rodriguez A, West M, Yadav D, Heim R, Fong JJ, and Garcia-Guzman M
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- Humans, Animals, Mice, Phototherapy methods, Disease Models, Animal, Cell Line, Tumor, Tumor Microenvironment, Immunotherapy methods, Neoplasms therapy
- Abstract
The complex immunosuppressive nature of solid tumor microenvironments poses a significant challenge to generating efficacious and durable anticancer responses. Photoimmunotherapy is a cancer treatment strategy by which an antibody is conjugated with a non-toxic light-activatable dye. Following administration of the conjugate and binding to the target tumor, subsequent local laser illumination activates the dye, resulting in highly specific target cell membrane disruption. Here we demonstrate that photoimmunotherapy treatment elicited tumor necrosis, thus inducing immunogenic cell death characterized by the release of damage-associated molecular patterns (DAMPs). Photoimmunotherapy-killed tumor cells activated dendritic cells (DC), leading to the production of proinflammatory cytokines, T cell stimulation, priming antigen-specific T cells, and durable memory T cell responses, which led complete responder mice to effectively reject new tumors upon rechallenge. PD-1 blockade in combination with photoimmunotherapy enhanced overall anticancer efficacy, including against anti-PD-1-resistant tumors. The combination treatment also elicited abscopal anticancer activity, as observed by reduction of distal, non-illuminated tumors, further demonstrating the ability of photoimmunotherapy to harness local and peripheral T cell responses. With this work we therefore delineate the immune mechanisms of action for photoimmunotherapy and demonstrate the potential for cancer-targeted photoimmunotherapy to be combined with other immunotherapy approaches for augmented, durable anticancer efficacy. Moreover, we demonstrate responses utilizing various immunocompetent mouse models, as well as in vitro data from human cells, suggesting broad translational potential., (© 2022. The Author(s).)
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- 2023
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215. The Good Immigrants : How the Yellow Peril Became the Model Minority
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Hsu, Madeline Y., CHAFE, WILLIAM, GERSTLE, GARY, GORDON, LINDA, ZELIZER, JULIAN, Hsu, Madeline Y., CHAFE, WILLIAM, GERSTLE, GARY, GORDON, LINDA, and ZELIZER, JULIAN
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- 2015
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216. Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial.
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Ruperto N, Brunner HI, Synoverska O, Ting TV, Mendoza CA, Spindler A, Vyzhga Y, Marzan K, Grebenkina L, Tirosh I, Imundo L, Jerath R, Kingsbury DJ, Sozeri B, Vora SS, Prahalad S, Zholobova E, Butbul Aviel Y, Chasnyk V, Lerman M, Nanda K, Schmeling H, Tory H, Uziel Y, Viola DO, Posner HB, Kanik KS, Wouters A, Chang C, Zhang R, Lazariciu I, Hsu MA, Suehiro RM, Martini A, and Lovell DJ
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- Administration, Oral, Adolescent, Child, Child, Preschool, Humans, Treatment Outcome, Arthritis, Juvenile drug therapy, Janus Kinase Inhibitors therapeutic use, Piperidines therapeutic use, Pyrimidines therapeutic use
- Abstract
Background: Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA)., Methods: This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434., Findings: Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study., Interpretation: The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections., Funding: Pfizer., Competing Interests: Declaration of interests NR has received honoraria for consultancy fees or speaker bureaus from Ablynx, AstraZeneca/MedImmune, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, EMD Serono, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, R-Pharm, Sanofi, Servier, Sinergie, and Sobi. The IRCCS Istituto Giannina Gaslini, where NR works as a full-time public employee, has received contributions from the following pharmaceutical companies in the past 3 years: Bristol-Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, and Sobi; this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any involvement of third parties. HIB has received research grants from Bristol-Myers Squibb, MedImmune, Novartis, and Pfizer; is an employee of Cincinnati Children's Hospital Medical Center; has received consulting fees or other remuneration from AbbVie, AstraZeneca/MedImmune, Bayer, Biocon, Boehringer Ingelheim, Janssen, Lilly, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and R-Pharm; and is a member of speaker bureaus for GlaxoSmithKline, Novartis, and Roche. OS is a member of a speaker bureau for Sanofi. AS is a member of a speaker bureau for Eli Lilly. KM has received research grants from Novartis and Pfizer. SP has received consulting fees or other remuneration from Novartis. EZ is a member of speaker bureaus for AbbVie, Novartis, Pfizer, and Roche. ML has received research grants from Amgen. KN has received research grants from Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Patient-Centered Outcomes Research Institute, and Roche. HS has received research grants from Bristol-Myers Squibb, Janssen, Pfizer, Roche, Sanofi, and USB Bioscience. YU is a member of a speaker bureau for Pfizer. DOV has received research grants from Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and Pfizer; and is a member of speaker bureaus for AbbVie and Bristol-Myers Squibb. HBP, KSK, AW, CC, RZ, M-AH, and RMS are employees and stockholders of Pfizer. IL is an employee of IQVIA, who were paid contractors to Pfizer in the development of this manuscript and in providing statistical support. AM has received consulting fees or other remuneration from Aurinia, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Janssen, and Pfizer. DJL's institution, the Cincinnati Children's Hospital Medical Center, has received research grants from Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Roche, and UCB; and has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Roche, Takeda, and UCB for the work of DJL. DJL is a Data Safety and Monitoring Board chairperson for Forest Research and the National Institutes of Health. All otjer authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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217. Correction to: Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.
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Hall R, Lebwohl MG, Bushmakin AG, Simpson EL, Gooderham MJ, Wollenberg A, Gater A, Wells JR, Cappelleri JC, Hsu MA, Papacharalambous J, Peeva E, Tallman AM, Zhang W, and Chen L
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- 2021
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218. Chinese Americans and the Politics of Race and Culture
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Chan, Sucheng, Hsu, Madeline Y., Chan, Sucheng, and Hsu, Madeline Y.
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- 2008
219. Safety and efficacy of tofacitinib up to 48 months in patients with active psoriatic arthritis: final analysis of the OPAL Balance long-term extension study.
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Nash P, Coates LC, Fleishaker D, Kivitz AJ, Mease PJ, Gladman DD, FitzGerald O, Wang C, Wu J, Hsu MA, Menon S, Fallon L, and Kanik KS
- Abstract
Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis. Here we report the final analysis of Oral Psoriatic Arthritis Trial (OPAL) Balance, a 36-month long-term extension study, with a 12-month methotrexate withdrawal substudy, that assessed tofacitinib safety, tolerability, and efficacy in patients with active psoriatic arthritis., Methods: For this open-label, long-term extension study, which was run at 124 centres in 16 countries, eligible patients had participated in the OPAL Broaden or OPAL Beyond phase 3 studies. Patients could enter OPAL Balance up to 3 months after completing one of the qualifying studies or discontinuing for reasons other than an adverse event related to study drug. In OPAL Balance, patients received open-label tofacitinib 5 mg twice daily, with increases to 10 mg twice daily for inadequate symptom control allowed from month 1, and reductions to 5 mg twice daily allowed thereafter for safety. Specific conventional synthetic disease-modifying antirheumatic drugs could be continued concomitantly. The primary endpoints were incidence and severity of adverse events, the incidence of laboratory abnormalities, and changes from baseline in laboratory parameters. Participants who were eligible could enter the randomised, double-blind, methotrexate withdrawal substudy (open-label tofacitinib 5 mg twice daily plus either masked placebo or masked methotrexate); safety data from which are included here (up to month 48). Efficacy was reported up to month 36 (substudy data excluded). The risk period for safety outcomes was the time from treatment exposure to the last dose plus 28 days or date of last observation. OPAL Balance is registered with ClinicalTrials.gov (NCT01976364) and is now complete., Findings: Between Feb 17, 2014, and March 28, 2016, 686 patients were enrolled and given tofacitinib 5 mg or 10 mg twice daily (179 patients were treated in the substudy and 453 [66%] of 686 completed the long-term extension study or substudy; mean treatment duration 794·6 days [SD 329·2] in long-term extension study, 879·0 days [396·6] in long-term extension study plus substudy). The mean age of participants in the all tofacitinib group was 48·8 years (SD 11·8) and 370 (54%) of 686 participants were female. Up to month 48, 574 (84%) of 686 participants reported all-cause adverse events, 115 (17%) reported serious adverse events, and 78 (11%) discontinued due to an adverse event. Six patients died, one within the risk period (incidence of 0·1 patients with events [95% CI 0·0-0·3] per 100 person-years). The incidences of adverse events of special interest, reported as number of patients with events per 100 person-years, included: 1·7 (1·2-2·5) for herpes zoster (non-serious and serious); 1·0 (0·6-1·6) for serious infections; 0·4 (0·1-0·8) for opportunistic infections; 0·7 (0·4-1·2) for malignancies (excluding non-melanoma skin cancer [NMSC]); 0·9 (0·5-1·5) for NMSC; 0·2 (0·1-0·6) for major adverse cardiovascular events; 0·1 (0·0-0·3) for pulmonary embolism; and 0·4 (0·1-0·8) for arterial thromboembolism. No deep vein thromboses occurred. Laboratory parameter changes were as expected with treatment. Efficacy was sustained up to month 36., Interpretation: This analysis supports the long-term safety (up to 48 months) and efficacy (up to 36 months) of tofacitinib in patients with psoriatic arthritis, which were consistent with previous phase 3 studies., Funding: Pfizer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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220. Relationships between psoriatic arthritis composite measures of disease activity with patient-reported outcomes in phase 3 studies of tofacitinib.
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Coates LC, Bushmakin AG, FitzGerald O, Gladman DD, Fallon L, Cappelleri JC, Hsu MA, and Helliwell PS
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- Humans, Patient Reported Outcome Measures, Piperidines, Pyrimidines, Quality of Life, Severity of Illness Index, Treatment Outcome, Antirheumatic Agents therapeutic use, Arthritis, Psoriatic diagnosis, Arthritis, Psoriatic drug therapy
- Abstract
Background: In psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures., Methods: Data from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0-7; scores ≥5 indicated MDA). For PASDAS (score range, 0-10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient's Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models., Results: Similar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (- 6.7 mm, - 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (- 2.8, - 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively., Conclusions: Linear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA., Trial Registration: ClinicalTrials.gov, NCT01877668 . Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439 . Registered on June 18, 2013.
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- 2021
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221. Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.
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Hall R, Lebwohl MG, Bushmakin AG, Simpson EL, Gooderham MJ, Wollenberg A, Gater A, Wells JR, Cappelleri JC, Hsu MA, Papacharalambous J, Peeva E, Tallman AM, Zhang W, and Chen L
- Abstract
Introduction: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties., Methods: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib., Results: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively., Conclusions: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.
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- 2021
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222. Tofacitinib as monotherapy following methotrexate withdrawal in patients with psoriatic arthritis previously treated with open-label tofacitinib plus methotrexate: a randomised, placebo-controlled substudy of OPAL Balance.
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Nash P, Mease PJ, Fleishaker D, Wu J, Coates LC, Behrens F, Gladman DD, Kivitz AJ, Wei JC, Shirinsky I, Menon S, Romero AB, Fallon L, Hsu MA, Wang C, and Kanik KS
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Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. This study evaluated the efficacy and safety of tofacitinib 5 mg twice daily monotherapy after methotrexate withdrawal., Methods: OPAL Balance was an open-label, long-term extension study of tofacitinib in patients with psoriatic arthritis who participated in the OPAL Broaden and OPAL Beyond phase 3 studies. This 12-month, randomised, double-blind, placebo-controlled, methotrexate withdrawal substudy (50 centres, 14 countries) included patients from OPAL Balance who completed tofacitinib treatment for 24 months or more (≥3 months' stable tofacitinib 5 mg twice daily) and were receiving methotrexate (7·5-20 mg/week). Patients were blindly randomised (1:1) using interactive response technology and received open-label tofacitinib 5 mg twice daily with either placebo (tofacitinib 5 mg twice daily plus placebo group) or continued methotrexate (tofacitinib 5 mg twice daily plus methotrexate group). Patients were masked to placebo or methotrexate, with identical capsules used. Coprimary endpoints were changes from substudy baseline in psoriatic arthritis disease activity score (PASDAS) and health assessment questionnaire-disability index (HAQ-DI) at month 6 in all randomised patients with one or more substudy drug dose. Safety was assessed throughout. No specific statistical hypothesis (either superiority or non-inferiority) was tested. The study (OPAL Balance) is registered with ClinicalTrials.gov (NCT01976364) and is complete., Findings: Between Oct 30, 2017, and May 20, 2019, 180 patients from OPAL Balance who were eligible for the substudy were randomly assigned to treatment (90 patients received tofacitinib 5 mg twice daily plus placebo and 89 patients assigned to tofacitinib plus methotrexate; one patient was not treated because of randomisation error). At month 6, least squares mean (LSM) changes in PASDAS were 0·23 (SE 0·08) for tofacitinib 5 mg twice daily plus placebo and 0·14 (0·08) for tofacitinib 5 mg twice daily plus methotrexate (treatment difference LSM 0·09 [95% CI -0·13 to 0·31]), and changes in HAQ-DI were 0·04 (0·03) and 0·02 (0·03), respectively (treatment difference 0·03 [-0·05 to 0·10]). Rates of adverse events, discontinuations because of adverse events, adverse events of special interest, and laboratory changes were generally similar between treatment groups, although liver enzyme elevations were more common with tofacitinib 5 mg twice daily plus methotrexate than tofacitinib 5 mg twice daily plus placebo. Flares of worsening symptoms was reported in one (1%) of 90 patients in the tofacitinib 5 mg twice daily plus placebo group (recorded as psoriatic arthropathy)., Interpretation: Some patients with psoriatic arthritis who are stable on tofacitinib 5 mg twice daily with background methotrexate might be able to discontinue methotrexate without clinically meaningful changes in disease activity and safety., Funding: Pfizer Inc., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2021
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223. Tofacitinib in psoriatic arthritis patients: skin signs and symptoms and health-related quality of life from two randomized phase 3 studies.
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Merola JF, Papp KA, Nash P, Gratacós J, Boehncke WH, Thaçi D, Graham D, Hsu MA, Wang C, Wu J, and Young P
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- Adult, Double-Blind Method, Humans, Piperidines, Pyrimidines therapeutic use, Pyrroles therapeutic use, Quality of Life, Treatment Outcome, Arthritis, Psoriatic drug therapy, Psoriasis drug therapy
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Background: Psoriatic arthritis (PsA) is a chronic, systemic immune-mediated inflammatory musculoskeletal disease. The onset of dermatologic symptoms often precedes rheumatic manifestations. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA that has been shown to improve dermatologic symptoms in patients with PsA., Objectives: To investigate the efficacy of tofacitinib in improving dermatologic endpoints in adult patients with active PsA., Methods: This analysis included data from two placebo-controlled, double-blind, phase 3 studies in patients with active PsA and an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) who were tumor necrosis factor inhibitor (TNFi)-naïve (OPAL Broaden; NCT01877668) or an IR to ≥1 TNFi (OPAL Beyond; NCT01882439). Patients had active plaque psoriasis at screening and received a stable dose of one csDMARD during the study. Patients were randomized to tofacitinib 5 mg twice daily (BID), 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only) or placebo (to Month 3). Dermatologic endpoints: Psoriasis Area and Severity Index (PASI) total score; PASI90 overall; PASI75 and PASI90 by baseline PASI severity; Physician's Global Assessment of Psoriasis; Nail Psoriasis Severity Index; Dermatology Life Quality Index total and sub-dimension scores; Itch Severity Item; and Patient's Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question., Results: In patients with active PsA, including those stratified by mild or moderate/severe dermatologic symptoms, greater improvements from baseline and percentage of responders were observed in tofacitinib-treated patients vs. placebo for the majority of analyzed dermatologic endpoints at Months 1 and 3, and improvements were maintained to Month 12 in OPAL Broaden and Month 6 in OPAL Beyond. Similar effects were observed in adalimumab-treated patients vs. placebo in OPAL Broaden across dermatologic endpoints., Conclusions: Tofacitinib provides a treatment option for patients with active PsA, including the burdensome dermatologic symptoms of PsA., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2020
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224. Safety and Efficacy of Tofacitinib in Patients with Active Psoriatic Arthritis: Interim Analysis of OPAL Balance, an Open-Label, Long-Term Extension Study.
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Nash P, Coates LC, Kivitz AJ, Mease PJ, Gladman DD, Covarrubias-Cobos JA, FitzGerald O, Fleishaker D, Wang C, Wu J, Hsu MA, Menon S, Fallon L, Romero AB, and Kanik KS
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Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). We report the interim safety, tolerability, and efficacy of tofacitinib in PsA patients in OPAL Balance, a 3-year, open-label, long-term extension study (data cut-off: August 2017; database not locked, data may change)., Methods: Eligible patients from two phase (P) 3 (P3) tofacitinib PsA studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered OPAL Balance ≤ 3 months after completing the P3 study or discontinuing for reasons other than study-drug-related adverse events (AEs). Patients received open-label tofacitinib 5 mg twice daily (BID), with adjustments to 10 mg BID permitted post-month (M) 1. Certain concomitant conventional synthetic disease-modifying antirheumatic drugs were allowed. Primary endpoints were incidence/severity of AEs and laboratory abnormalities, and changes from baseline in laboratory parameters (reported up to M36 and M30, respectively). Efficacy (clinical/patient-reported outcomes) was reported through M30., Results: A total of 686 patients were treated; at data cut-off, 68.2% remained in the study. Mean (range) treatment duration was 641 (1-1032) days; total treatment duration was 1153.2 patient-years. By M36, 79.6, 13.8, and 8.6% of patients reported AEs, serious AEs, and discontinuations due to AEs, respectively. Five deaths occurred; one within the risk period (incidence rate [IR; patients with events/100 patient-years] 0.1). IRs for AEs of special interest were: all (non-serious and serious) herpes zoster, 1.7; serious infections, 0.9; opportunistic infections, 0.3 (all disseminated/multi-dermatomal herpes zoster); malignancies excluding non-melanoma skin cancer (NMSC), 0.8; NMSC, 1.0; major adverse cardiovascular events, 0.3; pulmonary embolisms, 0.1; and arterial thromboembolisms, 0.4. No patients had deep vein thrombosis. Alanine aminotransferase and aspartate aminotransferase levels were elevated ≥ 3-fold the upper limit of normal in 4.0 and 2.2% of patients, respectively. Changes in laboratory parameters were generally stable over time, although lymphocyte counts decreased slightly. Efficacy was maintained through M30., Conclusions: In this interim analysis of OPAL Balance, tofacitinib safety and efficacy in patients with PsA appeared to be consistent with those of the P3 studies. Efficacy was maintained over time., Trial Registration: ClinicalTrials.gov identifier: NCT01976364.
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- 2020
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225. Network Meta-Analysis of Tofacitinib, Biologic Disease-Modifying Antirheumatic Drugs, and Apremilast for the Treatment of Psoriatic Arthritis.
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Gladman DD, Orbai AM, Gomez-Reino J, Chang-Douglass S, Leoncini E, Burton HE, Kanik KS, Romero AB, Cappelleri JC, and Hsu MA
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Background: Tofacitinib and other new treatments approved for use in psoriatic arthritis have only recently been included in psoriatic arthritis treatment guidelines, and studies evaluating the relative efficacy of available therapies are important to inform treatment decisions by healthcare professionals., Objective: To perform a network meta-analysis to evaluate the efficacy and safety profiles of tofacitinib, biologic disease-modifying antirheumatic drugs (bDMARDs), and apremilast in patients with psoriatic arthritis naïve to tumor necrosis factor inhibitor therapy (TNFi-naïve) or with an inadequate response (TNFi-IR)., Methods: A systematic literature review used searches of MEDLINE, Embase, and The Cochrane Library on October 9, 2017. Randomized controlled trials including adult patients with psoriatic arthritis receiving treatment administered as monotherapy or with conventional synthetic DMARDs were selected. Efficacy outcomes included American College of Rheumatology 20 response, change from baseline in Health Assessment Questionnaire-Disability Index, ≥75% improvement in Psoriasis Area and Severity Index, and change from baseline in Dactylitis Severity Score and Leeds Enthesitis Index. Treatment effects were evaluated during placebo-controlled phases, using a binomial logit model for binary outcomes and a normal identify link model for other outcomes. Discontinuations due to adverse events and serious infection events were assessed as safety outcomes., Results: The network meta-analysis included 24 published randomized controlled trials, of which 13 enrolled TNFi-naïve patients only, 3 enrolled TNFi-IR patients only, and 8 enrolled both TNFi-naïve and TNFi-IR patients. Placebo-controlled treatment durations ranged from 12 to 24 weeks. Indirect comparisons showed tofacitinib 5 and 10 mg BID to have similar efficacy compared with most bDMARDs and apremilast in improving joint symptoms (based on American College of Rheumatology 20 response), and with some bDMARDs in improving skin symptoms (based on Psoriasis Area and Severity Index) (tofacitinib 10 mg BID only in TNFi-IR) in patients with psoriatic arthritis who were TNFi-naïve or TNFi-IR. Results also showed that, compared with placebo, the improvement in physical functioning (based on Health Assessment Questionnaire-Disability Index) with tofacitinib 5 and 10 mg BID was similar to that observed with most bDMARDs and apremilast in TNFi-naïve patients, and similar to that observed with all bDMARDs with available data in the TNFi-IR population. Improvements in Dactylitis Severity Score and Leeds Enthesitis Index scores were comparable between treatments. Tofacitinib 5 and 10 mg BID were median-ranked 8 and 15, respectively, for discontinuation due to any adverse events, and 5 and 16, respectively, for a serious infection event out of a total of 20 treatments in the network (lower numbers are more favorable)., Conclusions: Tofacitinib provides an additional treatment option for patients with psoriatic arthritis, both in patients naïve to TNFi and in those with TNFi-IR. ( Curr Ther Res Clin Exp. 2020; 81:XXX-XXX)., (© 2020 The Authors.)
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- 2020
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226. Costs and Health Outcomes Associated with Tofacitinib Treatment for Active Psoriatic Arthritis in the United States.
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Bungey G, Chang-Douglass S, Hsu MA, Cappelleri JC, Young P, and Woolcott J
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- Arthritis, Psoriatic drug therapy, Arthritis, Psoriatic epidemiology, Female, Humans, Male, Piperidines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Randomized Controlled Trials as Topic economics, Treatment Outcome, United States epidemiology, Arthritis, Psoriatic economics, Decision Trees, Health Care Costs trends, Models, Economic, Piperidines economics, Protein Kinase Inhibitors economics, Pyrimidines economics
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Background: Psoriatic arthritis (PsA) is a chronic progressive inflammatory condition associated with significant direct and indirect costs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Economic evaluations, alongside clinical data, help inform papers and formulary decisions in the United States., Objective: To evaluate outcomes and costs of including tofacitinib in treatment strategies for PsA from a third-party U.S. payer perspective, using a health economic model., Methods: A decision tree model was developed to evaluate treatment sequences (up to 4 lines of advanced PsA therapy) with or without tofacitinib. Patients included in the model had active PsA and a previous inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor inhibitor (TNFi) therapy. The analysis time horizon was 2 years; decision points for continuing/switching treatments occurred quarterly, based on clinical response (assessed using the primary rheumatoid measure of efficacy, American College of Rheumatology [ACR]20 response only) and adverse drug reactions (ADRs). Costs included those related to ADRs and drug acquisition, monitoring, and administration. Other endpoints of PsA, such as assessment of enthesitis and dactylitis, were not integrated into the model., Results: Treatment strategies including tofacitinib were associated with cost savings versus strategies without tofacitinib across all modeled scenarios, with an estimated 2-year cost saving of up to $8,454,858, based on 1 million insurants. Similarly, costs per member per month and per ACR20 responder were lower for sequences including tofacitinib versus sequences without. These savings arose because of lower ADR and drug acquisition/administration costs for sequences including tofacitinib. Deterministic sensitivity analyses showed these results to be robust., Conclusions: This analysis suggests that including tofacitinib in the treatment of active PsA in csDMARD-IR or TNFi-IR patients is a cost-saving alternative to sequences without tofacitinib, potentially reducing costs for PsA advanced therapies by up to $8.4 million over 2 years for payers insuring 1 million individuals., Disclosures: This work was sponsored by Pfizer Inc. Bungey is an employee of Decision Resources Group, which received financial support from Pfizer Inc to develop the treatment-cost model used in the development of this manuscript. Chang-Douglass was an employee of Decision Resources Group at the time of the analysis. During development of this publication, Chang-Douglass started a role at the National Institute for Health and Care Excellence (NICE). The publication only reflects her views and does not reflect the views of NICE. Hsu, Cappelleri, Young, and Woolcott are employees of Pfizer Inc and own stock or stock options in Pfizer Inc. The data reported in this manuscript have been previously presented at the American College of Rheumatology Annual Scientific Meeting; October 19-24, 2018; Chicago, IL, and the AMCP Annual Meeting and Expo; March 25-28, 2019; San Diego, CA.
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- 2020
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227. Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.
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Ogdie A, de Vlam K, McInnes IB, Mease PJ, Baer P, Lukic T, Gruben D, Kwok K, Wang C, Hsu MA, and Maniccia A
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- Adult, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Antirheumatic Agents therapeutic use, Case-Control Studies, Female, Humans, Male, Middle Aged, Pain drug therapy, Pain etiology, Pain prevention & control, Pain Management, Pain Measurement methods, Patient Reported Outcome Measures, Piperidines administration & dosage, Placebos administration & dosage, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors therapeutic use, Pyrimidines administration & dosage, Quality of Life, Treatment Outcome, Tumor Necrosis Factor Inhibitors therapeutic use, Arthritis, Psoriatic drug therapy, Arthritis, Rheumatoid drug therapy, Piperidines therapeutic use, Pyrimidines therapeutic use, Spondylitis, Ankylosing drug therapy
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Objective: To describe the efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) in a post-hoc analysis of randomised controlled trials., Methods: Data were collected from patients in seven tofacitinib studies: six phase III (four RA, two PsA) and one phase II study (AS), and grouped into five analysis populations based on rheumatic disease diagnosis and category of prior inadequate response (IR) to treatment: conventional synthetic disease-modifying antirheumatic drugs-IR (RA and PsA), tumour necrosis factor inhibitors-IR (RA and PsA), or non-steroidal anti-inflammatory drugs-IR (AS). Only patients who received tofacitinib 5 or 10 mg twice daily or placebo were included. Pain assessments included: Patient's Assessment of Arthritis Pain, Short-Form Health Survey 36v2 Question (Q)7 and Bodily Pain domain, Ankylosing Spondylitis Quality of Life Q9 and Q14, EuroQol Five Dimensions Pain/Discomfort dimension and Bath Ankylosing Spondylitis Disease Activity Index Q2 and Q3. Data were reported to month 6 (placebo to month 3) in the RA and PsA populations, and week 12 (tofacitinib and placebo) in the AS population., Results: Overall, 3330 patients were included in this analysis. In the RA and PsA populations, pain improvements in tofacitinib-treated patients compared with placebo were observed at the earliest time point assessed and at month 3 (maintained to month 6). In the AS population, pain improvements compared with placebo were observed at week 12., Conclusion: Tofacitinib was associated with rapid and sustained improvements across multiple pain measures in patients with inflammatory rheumatic musculoskeletal diseases., Competing Interests: Competing interests: AO has served as a consultant for AbbVie, Amgen, BMS, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc and Takeda, and has received grant support from Novartis and Pfizer Inc. KdV has received consulting fees or other remuneration from Eli Lilly and Pfizer Inc, and has participated in a trial with Galapagos. IBM has received research grants from Celgene, Janssen, Novartis, Pfizer Inc, Roche and UCB, and has received consulting fees or other remuneration from AbbVie, Celgene, Janssen, Novartis and UCB. PJM has received research grants from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun Pharmaceutical and UCB, has received consulting fees or other remuneration from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun Pharmaceutical and UCB, and is on the speakers’ bureau for AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Novartis, Pfizer Inc and UCB. PB has received consulting fees or other remuneration from AbbVie, Amgen, Eli Lilly, Johnson and Johnson, Novartis, Paladin, Sanofi-Genzyme and Takeda, and is on the speakers’ bureau for Amgen, Eli Lilly, Janssen and Pfizer Inc. TL, DG, KK, CW, and M-AH are employees and shareholders of Pfizer Inc. AM is a shareholder, and was an employee, of Pfizer Inc during the time of this analysis., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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228. Retraction Note to: Content validity and psychometric evaluation of functional assessment of chronic illness therapy-fatigue in patients with psoriatic arthritis.
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Cella D, Wilson H, Shalhoub H, Revicki DA, Cappelleri JC, Bushmakin AG, Kudlacz E, and Hsu MA
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The publisher has retracted this article [1] because the incorrect version of the article was published in error.
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229. Content validity and psychometric evaluation of Functional Assessment of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis.
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Cella D, Wilson H, Shalhoub H, Revicki DA, Cappelleri JC, Bushmakin AG, Kudlacz E, and Hsu MA
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Background: To evaluate the measurement properties (e.g., content validity, reliability, and ability to detect change) of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale in patients with active psoriatic arthritis (PsA)., Methods: One-on-one semi-structured qualitative interviews with adult patients with active PsA evaluated the content validity of FACIT-Fatigue. Quantitative measurement properties were evaluated using data from phase III tofacitinib randomized controlled trials (RCTs) in PsA: OPAL Broaden (NCT01877668) and OPAL Beyond (NCT01882439)., Results: Of 12 patients included in the qualitative study, 2 (17%) had mild, 8 (67%) had moderate, and 2 (17%) had severe PsA disease activity; 7 (58%) attributed fatigue to PsA, and 7 (58%) rated fatigue as important or extremely important. Most patients considered the FACIT-Fatigue items relevant to their PsA experience, and understood item content and response options as intended. In the psychometric analysis of RCT data, a second-order confirmatory factor model fit the data well (Bentler's Comparative Fit Index ≥0.92). FACIT-Fatigue demonstrated good internal consistency (Cronbach's coefficient α ≥ 0.90), test-retest reliability (Intraclass Correlation Coefficient ≥ 0.80) and a strong correlation with SF-36 Vitality (r > 0.80). A robust relationship between disease activity (based on Patient's Global Assessment of Psoriasis and Arthritis) and FACIT-Fatigue was observed (effect sizes > 1.4), with clinically important difference for the FACIT-Fatigue total score estimated as 3.1 points, and the responder definition estimated as a 4-point improvement for FACIT-Fatigue total score., Conclusion: Fatigue was confirmed to be an important symptom to patients with PsA, and FACIT-Fatigue was found to be a reliable and valid measure in this population.
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- 2019
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230. Effect of tofacitinib on patient-reported outcomes in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors in the phase III, randomised controlled trial: OPAL Beyond.
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Strand V, de Vlam K, Covarrubias-Cobos JA, Mease PJ, Gladman DD, Chen L, Kudlacz E, Wu J, Cappelleri JC, Hendrikx T, and Hsu MA
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- Arthritis, Psoriatic diagnosis, Biomarkers, Female, Humans, Male, Patient Reported Outcome Measures, Piperidines administration & dosage, Piperidines adverse effects, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Pyrimidines administration & dosage, Pyrimidines adverse effects, Pyrroles administration & dosage, Pyrroles adverse effects, Severity of Illness Index, Treatment Outcome, Tumor Necrosis Factor Inhibitors therapeutic use, Arthritis, Psoriatic drug therapy, Piperidines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Pyrroles therapeutic use
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Objectives: Tofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). Patient-reported outcomes (PROs) were evaluated in patients with PsA with inadequate responses to tumour necrosis factor inhibitors (TNFi-IR) in a 6-month, phase III randomised controlled trial (OPAL Beyond [NCT01882439])., Methods: Patients (N=394) received tofacitinib 5 or 10 mg twice daily or placebo (advancing to tofacitinib 5 or 10 mg twice daily at month 3). Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences and scores ≥normative values were determined in Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level (EQ-5D-3L), EQ-VAS and Ankylosing Spondylitis Quality of Life (ASQoL). Nominal p values are without multiple comparison adjustments., Results: At month 3, PtGA, Pain, PGJS, SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP), vitality and social functioning (SF) domains, FACIT-Fatigue Total score, EQ-5D-3L pain/discomfort, EQ-VAS and ASQoL scores exceeded placebo with both tofacitinib doses (role physical [RP] with 10 mg twice daily only; p≤0.05). Patients reporting improvements ≥MCID (%) in PtGA, PGJS, Pain, ASQoL and SF-36v2 PCS, PF, RP, BP, SF (both tofacitinib doses) exceeded placebo (p≤0.05)., Conclusion: TNFi-IR patients with PsA receiving tofacitinib reported statistically and clinically meaningful improvements in PROs versus placebo over 3 months, which were maintained to month 6. Despite lower baseline scores, these improvements were similar to the csDMARD-IR TNFi-naive OPAL Broaden trial., Competing Interests: Competing interests: VS has received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi and UCB. KdV is a consultant and advisory board member for Pfizer Inc. JAC-C is an investigator for Pfizer Inc. PJM has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc, Sun and UCB; has acted as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Sun, UCB and Zynerba; and has participated in speakers’ bureaus for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc and UCB. DDG has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc and UCB; and has acted as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc and UCB. EK, JW, JCC, and M-AH are shareholders and employees of Pfizer Inc. LC and TH are shareholders and were employees of Pfizer Inc during the time of this analysis.
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231. Tofacitinib or adalimumab versus placebo: patient-reported outcomes from OPAL Broaden-a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs.
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Strand V, de Vlam K, Covarrubias-Cobos JA, Mease PJ, Gladman DD, Graham D, Wang C, Cappelleri JC, Hendrikx T, and Hsu MA
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- Adalimumab administration & dosage, Adalimumab adverse effects, Adult, Antirheumatic Agents administration & dosage, Antirheumatic Agents adverse effects, Arthritis, Psoriatic diagnosis, Female, Humans, Male, Middle Aged, Patient Reported Outcome Measures, Piperidines administration & dosage, Piperidines adverse effects, Pyrimidines administration & dosage, Pyrimidines adverse effects, Pyrroles administration & dosage, Pyrroles adverse effects, Treatment Outcome, Adalimumab therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Psoriatic drug therapy, Piperidines therapeutic use, Pyrimidines therapeutic use, Pyrroles therapeutic use
- Abstract
Objectives: Tofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668])., Methods: Patients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments., Results: At month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab., Conclusion: csDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3., Competing Interests: Competing interests: VS has received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi and UCB. KdV is a consultant and advisory board member for Pfizer Inc. JAC-C is an investigator for Pfizer Inc. PJM has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc, Sun and UCB; has acted as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Sun, UCB and Zynerba; and has participated in speakers’ bureaus for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc and UCB. DDG has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc and UCB and has acted as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc and UCB. M-AH, DG, CW and JCC are shareholders and employees of Pfizer Inc. TH is a shareholder, and was an employee, of Pfizer Inc during the time of this analysis.
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- 2019
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232. Patient Preferences Associated with Therapies for Psoriatic Arthritis: A Conjoint Analysis.
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Xu Y, Sudharshan L, Hsu MA, Koenig AS, Cappelleri JC, Liu WF, Smith TW, and Pasquale MK
- Abstract
Background: As psoriatic arthritis (PsA) treatment choices continue to expand, it is important to consider patient preferences for treatment modalities for PsA. Involving patients in treatment decisions can influence adherence to treatment and outcomes of therapy., Objective: To determine patient preferences for medication attributes prescribed for patients with PsA., Methods: A choice-based conjoint survey was mailed to 2800 randomly selected patients with PsA who were enrolled in Humana Medicare and commercial plans. Patients had been diagnosed with PsA between January 1, 2012, and September 30, 2016. The medication attributes included in the survey were the medication route of administration, frequency of administration, ability to reduce daily joint pain and swelling, likelihood of serious infections, improvement in the patient's ability to perform daily activities, achieving clear or almost clear skin, and cost. Hierarchical Bayesian models were used to score patient preferences after adjusting for demographic and clinical characteristics. The mean attribute importance scores were used to rank patient preferences., Results: A total of 468 patients (258 with a Medicare plan and 210 with a commercial plan) completed the survey. The top 3 medication attributes for patients in Medicare plans were route of administration, cost, and improvement in the ability to perform daily activities. For patients in commercial plans, the top 3 medication attributes were cost, route of administration, and frequency of administration. Within the top 2 attributes for patients in both plans, the oral route of administration and lower cost were most preferred., Conclusion: Medication route of administration and cost were the 2 most important considerations for patients diagnosed with PsA who were enrolled in Medicare or commercial plans with Humana. As PsA treatment choices continue to expand, considering patient preferences may improve patient adherence and treatment outcomes and should be considered when making treatment decisions for this patient population.
- Published
- 2018
233. Disease-specific composite measures for psoriatic arthritis are highly responsive to a Janus kinase inhibitor treatment that targets multiple domains of disease.
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Helliwell P, Coates LC, FitzGerald O, Nash P, Soriano ER, Elaine Husni M, Hsu MA, Kanik KS, Hendrikx T, Wu J, and Kudlacz E
- Subjects
- Adalimumab administration & dosage, Female, Humans, Injections, Subcutaneous, Longitudinal Studies, Male, Piperidines administration & dosage, Pyrimidines administration & dosage, Pyrroles administration & dosage, Treatment Outcome, Antirheumatic Agents administration & dosage, Arthritis, Psoriatic diagnosis, Arthritis, Psoriatic drug therapy, Drug Delivery Systems methods, Janus Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors administration & dosage
- Abstract
Background: The multiple disease domains affected in psoriatic arthritis (PsA) may make composite endpoints appropriate for assessing changes in disease activity over time. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Data from two phase 3 studies of patients with PsA were used to evaluate the effect of tofacitinib on composite endpoints., Methods: Oral Psoriatic Arthritis triaL (OPAL) Broaden was a 12-month study of tumor necrosis factor inhibitor (TNFi)-naïve patients with an inadequate response to at least one conventional synthetic disease-modifying anti-rheumatic drug; OPAL Beyond was a 6-month study of patients with inadequate response to TNFi. Patients with active PsA received tofacitinib 5 or 10 mg doses twice daily (BID), adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only), or placebo advancing at month 3 to tofacitinib 5 or 10 mg BID. The disease-specific composites were Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). Change from baseline in composite endpoints was also assessed for minimal disease activity (MDA) responders versus non-responders., Results: Overall, 422 patients from OPAL Broaden and 394 patients from OPAL Beyond were treated. The mean changes from baseline to month 3 for tofacitinib 5 mg BID, tofacitinib 10 mg BID (standard error; effect size) were OPAL Broaden: PASDAS, -2.0 (0.14; 1.73), -2.4 (0.14; 2.4); DAPSA, -20.2 (1.72; 0.9), -24.4 (1.73; 1.23); and CPDAI, -2.9 (0.34; 1.03), -4.2 (0.36; 1.53); OPAL Beyond: PASDAS, -1.9 (0.14; 1.53), -2.1 (0.14; 1.84); DAPSA, -22.5 (1.67; 0.81), -21.0 (1.70; 0.84); and CPDAI, -3.3 (0.31; 1.41), -3.4 (0.31; 1.45). Greater changes from baseline to month 3 (P ≤0.05) were seen with both doses of tofacitinib versus placebo for all endpoints except CPDAI for tofacitinib 5 mg BID in OPAL Broaden. Effect sizes generally increased from 3 to 6 months. Mean changes from baseline were greater in MDA responders than MDA non-responders for all composite endpoints across all time points and treatments., Conclusions: This analysis suggests that disease-specific composite measures are appropriate for evaluating treatment efficacy on multiple disease domains in PsA., Trial Registration: OPAL Broaden: ClinicalTrials.gov Identifier: NCT01877668 , first posted June 12, 2013; OPAL Beyond: ClinicalTrials.gov Identifier: NCT01882439 , first posted June 20, 2013.
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- 2018
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234. The impact of multimorbidity on quality of life among midlife women: findings from a U.S. nationally representative survey.
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Lang K, Alexander IM, Simon J, Sussman M, Lin I, Menzin J, Friedman M, Dutwin D, Bushmakin AG, Thrift-Perry M, Altomare C, and Hsu MA
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- Adult, Comorbidity, Cross-Sectional Studies, Female, Health Behavior, Humans, Middle Aged, Surveys and Questionnaires, United States, Health Status Indicators, Osteoporosis epidemiology, Quality of Life, Urinary Incontinence epidemiology, Vaginal Diseases epidemiology
- Abstract
Background: Little is known about the prevalence and cumulative burden of coexisting health conditions including chronic joint and muscular pain, urinary incontinence (UI), depression, osteoporosis risk, moderate/severe vasomotor symptoms, and vulvar/vaginal atrophy (VVA). We surveyed a nationally representative U.S. sample of midlife (age 40-64 years) women to ascertain the prevalence, general health-related quality of life (HRQoL), and health-seeking behaviors associated with these six conditions., Methods: This cross-sectional, telephone survey collected data from a sample of English- and Spanish-speaking U.S. women. The survey contained demographic and menopausal status questions, and also five condition-specific symptom/disease risk-screening instruments. The EuroQol 5 dimensions (EQ-5D) questionnaire was used to measure HRQoL. Health-seeking behavior was measured based on clinician discussion of and recent treatment for each condition., Results: Three thousand fifty eight women (mean age 53.4 years) completed the survey. The majority were white (75.6%), married (60.5%), employed full- or part-time (59.0%), and postmenopausal (69.8%; based on self-report). The prevalence [95% confidence interval] of 0, 1, 2, and ≥3 conditions was 35.2% [33.5-36.9], 34.2% [32.5-35.9], 17.9% [16.6-19.3], and 12.7% [11.5-13.9], respectively. Osteoporosis risk (30.6%) was most prevalent, followed by VVA (27.8%) and UI (26.6%). UI and VVA coexisted most frequently (11.3%), followed by osteoporosis risk and VVA (9.8%). EQ-5D scores decreased with increasing number of illnesses (0, 1, 2, and ≥3 conditions, means: 0.92, 0.87, 0.77, 0.61, respectively; p<0.01). Health-seeking behavior varied by condition., Conclusion: Over 25% of women surveyed had multiple coexisting conditions. Lower HRQoL was associated with multiple conditions and with each added condition.
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- 2015
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235. Predictors of functional improvement in employed adults with major depressive disorder treated with desvenlafaxine.
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Lam RW, Endicott J, Hsu MA, Fayyad R, Guico-Pabia C, and Boucher M
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- Adult, Aged, Antidepressive Agents adverse effects, Canada, Cyclohexanols adverse effects, Depressive Disorder, Major physiopathology, Depressive Disorder, Major psychology, Desvenlafaxine Succinate, Diagnostic and Statistical Manual of Mental Disorders, Double-Blind Method, Efficiency drug effects, Employment, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Neurotransmitter Uptake Inhibitors adverse effects, Psychiatric Status Rating Scales, Self Report, Severity of Illness Index, Time Factors, United States, Young Adult, Antidepressive Agents therapeutic use, Cyclohexanols therapeutic use, Depressive Disorder, Major drug therapy, Neurotransmitter Uptake Inhibitors therapeutic use
- Abstract
We carried out a secondary analysis of a double-blind, placebo-controlled trial of desvenlafaxine for major depressive disorder (MDD) to explore the associations between depressive symptoms and subtypes, and functional outcomes, including work functioning. Employed outpatients with MDD were assigned randomly in a 2 : 1 ratio to receive desvenlafaxine 50 mg/day or placebo for 12 weeks. Analyses were carried out post-hoc with the intent-to-treat (ITT) sample (N=427) and a prospectively defined modified ITT sample (N=310), composed of patients with baseline 17-item Hamilton Rating Scale for Depression score of at least 20. Functional outcomes at week 12 included items and factors from the Montgomery-Åsberg Depression Rating Scale, Sheehan Disability Scale, and the Work Productivity and Activity Impairment questionnaire. In the modified ITT sample, but not in the ITT sample, desvenlafaxine-treated patients showed significantly greater improvement in several functional outcomes in the responder, nonanxious, and normal-energy patient subgroups. Improvement in the 17-item Hamilton Rating Scale for Depression total score at week 2 predicted change at week 12 in several functional outcomes. Functional improvement at 12 weeks was greater in subgroups of patients and was also significantly predicted by early improvement in depressive symptoms in employed patients with MDD treated with desvenlafaxine.
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- 2014
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236. Improvements in quality of life with desvenlafaxine 50mg/d vs placebo in employed adults with major depressive disorder.
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Endicott J, Lam RW, Hsu MA, Fayyad R, Boucher M, and Guico-Pabia CJ
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- Adult, Aged, Depression, Desvenlafaxine Succinate, Double-Blind Method, Employment, Female, Humans, Male, Middle Aged, Placebos, Quality of Life, Surveys and Questionnaires, Young Adult, Antidepressive Agents therapeutic use, Cyclohexanols therapeutic use, Depressive Disorder, Major drug therapy
- Abstract
Background: Diminished quality of life (QOL) is associated with major depressive disorder (MDD)., Methods: QOL was assessed in a post-hoc analysis of a double-blind, placebo-controlled trial. Employed adult outpatients with MDD were randomly assigned to 12 weeks of treatment with desvenlafaxine 50mg/d or placebo. Changes from baseline in the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) item scores at week 12 were analyzed using analysis of covariance with treatment, region, and baseline in the model. Correlations between change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score and Q-LES-Q scores were computed., Results: The intent-to-treat population included 427 patients. There were statistically significant improvements from baseline for desvenlafaxine vs placebo in 10 of 16 Q-LES-Q item scores (P values ≤0.0441). The percentage of patients with severe QOL impairment (≥2 SD below community norm) at week 12 was significantly lower for desvenlafaxine (46%) vs placebo (62%; P=0.0024; baseline: 95% and 94%, respectively). Change in Q-LES-Q total score was highly correlated with change in HAM-D17 score at week 12, LOCF (P<0.0001), and improvement in HAM-D17 total score at week 2 predicted change in Q-LES-Q total score at week 12 for the desvenlafaxine group (F=24.89; P<0.0001) but not placebo., Limitations: This analysis excluded patients who were unemployed, had severe comorbidities, and those taking multiple, concomitant medications., Conclusion: Improvement in QOL and depressive symptoms was significantly greater for employed depressed patients treated with desvenlafaxine vs placebo., (Copyright © 2014 Elsevier B.V. All rights reserved.)
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- 2014
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237. Impact of physician specialty on classification of physician-perceived patient severity for patients with osteoarthritis.
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Bailey J, Hawker GA, Wood R, Cappelleri JC, Higgins V, Joyce N, and Hsu MA
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- Age Factors, Aged, Body Mass Index, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Observer Variation, Osteoarthritis complications, Osteoarthritis diagnostic imaging, Physicians, Primary Care statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Radiography, Rheumatology statistics & numerical data, Surgeons statistics & numerical data, Osteoarthritis diagnosis, Severity of Illness Index, Specialization statistics & numerical data
- Abstract
Background: Physicians often classify patients' osteoarthritis (OA) severity subjectively. As treatment decisions are influenced by severity classifications, it is important to understand the factors that influence physicians' OA severity ratings. This research sought to empirically identify physician and patient characteristics that lead to a patient being perceived as having more severe OA., Methods: Data were analyzed from the OA IX Disease Specific Program, a large cross-sectional survey of OA physicians and patients in Germany, the UK, and USA between September 2011 and January 2012. Eligible, consenting physicians completed a Patient Record Form (PRF) for 10 consecutive OA patients. The PRF asked physicians to report the patient's demographics [age, gender, body mass index (BMI), ethnicity], their assessment of the patients' symptom severity, treatment, probability for surgery, to rate their overall OA severity (mild, moderate or severe) and the factors that had influenced the rating. Chi-squared tests and analysis of variance were used to identify patient characteristics that significantly impacted physicians' OA severity ratings. Controlling for the significant patient characteristics, we then examined the impact of physician specialty on physician's OA severity ratings. Finally, we investigated the differences in physician-reported factors that influenced the physicians' rating of patients' severity between physician specialties., Results: Three hundred and sixty-three physicians [220 primary care physicians (PCPs), 48 rheumatologists, 95 orthopedic surgeons] recruited 3561 patients. Patients with greater age and BMI, worse symptoms and greater health care use were given higher OA severity ratings. Controlling for these factors, orthopedic surgeons rated their OA patients as more severe than PCPs and rheumatologists [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI) 1.4-2.4]. Specialists (rheumatologists and orthopedic surgeons) were more likely than PCPs to use joint spaced narrowing based on X-ray and severity of joint deterioration radiographic severity to assess patients' OA severity (joint space narrowing: 79% and 78% vs 55%, P < 0.0001)., Conclusions: Patient age, BMI, presence and severity of symptoms and health care use significantly impacted physicians' OA severity ratings, but radiographic changes appeared to be given greater weight among orthopedic surgeons and rheumatologists than PCPs when assessing patient severity. Whether these differences translate into different treatment recommendations for similar patients is unknown, and warrants study., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
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- 2014
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238. Application of Resource Utilization in Dementia (RUD) instrument in a global setting.
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Wimo A, Gustavsson A, Jönsson L, Winblad B, Hsu MA, and Gannon B
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- Americas, Appointments and Schedules, Asia, Caregivers psychology, Caregivers statistics & numerical data, Cultural Characteristics, Data Collection methods, Europe, Expert Testimony, Humans, Office Visits statistics & numerical data, Patient Acceptance of Health Care statistics & numerical data, Patients psychology, Reproducibility of Results, Sleep, Terminology as Topic, Time Management, Workload statistics & numerical data, Alzheimer Disease economics, Health Resources statistics & numerical data, Surveys and Questionnaires
- Abstract
Background: The Resource Utilization in Dementia (RUD) questionnaire is the most widely used instrument for resource use data collection in dementia, enabling comparison of costs of care across countries with differing health care provisions. Recent feedback from payers questioned its face validity given that health care provisions have changed since the initial development of the RUD in 1998. The aim of this study was to update the RUD to improve its face validity in Alzheimer's disease (AD) clinical research and its utility for health care resource allocation., Methods: An extensive PubMed review was conducted of current relevant resource items in AD in 15 countries. The findings were complemented by interviews with local care providers and experts in dementia care and health economics. Their proposed revisions were discussed with five leading dementia experts in North and South America, northern and southern Europe, and Asia. A new version of the RUD was developed based on their recommendations., Results: RUD users identified a need for more information relevant to coverage decisions. Proposed revisions included changes to existing questions (e.g., to capture more accurately the number and type of health care visits) and the addition of new questions (e.g., on informal caregiver hours and the primary caregiver's hours of sleep)., Conclusion: Several minor changes were made to the RUD instrument to improve the accuracy and precision of the data while maintaining comparability with the original version and reflecting current medical practice. The RUD Complete Version 4.0 is now available for use in future AD clinical trials., (Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
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- 2013
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239. Other paradigms: health-related quality of life as a measure in cancer treatment: its importance and relevance.
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Trask PC, Hsu MA, and McQuellon R
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- Attitude to Health, Clinical Trials as Topic, Humans, Neoplasms therapy, Outcome Assessment, Health Care, Sickness Impact Profile, Treatment Outcome, Neoplasms psychology, Quality of Life, Surveys and Questionnaires standards
- Abstract
During the past 2 decades, there have been advances in the definition, measurement, and application in clinical trials and practice of health-related quality of life (HRQOL). In addition, the importance of bringing the patient's voice to medical decision making has been increasing. However, there remains some question as to the importance of the HRQOL construct in cancer treatment. This article addresses several issues related to HRQOL in oncology including (1) reasons for including HRQOL measurements in treatment studies, (2) the importance of HRQOL information in the absence of clinical therapeutic benefit, (3) determining clinical significance of HRQOL data, and (4) when it may not be important to measure HRQOL. HRQOL information can be a useful outcome of therapeutic benefit for patients undergoing cancer treatments, especially when it is associated with a clinical intervention such as additional supportive services, symptom management, and a new medicine that reduces tumor size or extends life. Moreover, it is important to establish the meaningful important difference levels on HRQOL questionnaires to trigger health professionals to begin, maintain, or end cancer interventions.
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- 2009
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240. Psychometric validation of the cancer therapy satisfaction questionnaire.
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Trask PC, Tellefsen C, Espindle D, Getter C, and Hsu MA
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- Adult, Aged, Aged, 80 and over, Data Interpretation, Statistical, Female, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Quality of Life, United States, Neoplasms psychology, Neoplasms therapy, Patient Satisfaction, Psychometrics, Surveys and Questionnaires
- Abstract
Purpose: To assess the domain structure and to evaluate the psychometric properties of the Cancer Therapy Satisfaction Questionnaire (CTSQ) and the relation between the CTSQ and health-related quality of life (HRQOL)., Methods: Three hundred sixty-one individuals with breast, colorectal, lung cancer, or melanoma who had received in the last 6 months or were currently receiving more than one cycle of chemo, biological, or hormonal therapy completed the 21-item CTSQ, with a random subsample of 88 patients completing it again 1 week later. Participants also completed quality of life, treatment satisfaction, and other self-reported questions on each occasion. Demographics, ECOG performance status, and clinical information were collected. CTSQ responses were submitted to multitrait analyses and exploratory factor analysis. Psychometric properties and the correlations between the CTSQ and the Quality of Life Questionnaire -- Core 30 (QLQ-C30) were evaluated., Results: Analyses revealed three domains with good psychometric properties: Feelings about Side Effects, Satisfaction with Therapy, and Expectations of Therapy. Correlations with the QLQ-C30 domains were low to moderate., Conclusion: The CTSQ is a newly developed 16-item patient-reported measure with strong psychometric properties and constructs not captured by the QLQ-C30. It can be used to evaluate cancer patients' experiences with intravenous and/or oral chemo, biological, and hormonal therapies.
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- 2008
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241. The orexin-1 antagonist SB-334867 blocks antipsychotic treatment emergent catalepsy: implications for the treatment of extrapyramidal symptoms.
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Rasmussen K, Hsu MA, Noone S, Johnson BG, Thompson LK, and Hemrick-Luecke SK
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- Animals, Behavior, Animal drug effects, Locomotion drug effects, Male, Naphthyridines, Olanzapine, Orexins, Prolactin metabolism, Rats, Rats, Sprague-Dawley, Urea pharmacology, Urea therapeutic use, Antipsychotic Agents antagonists & inhibitors, Basal Ganglia Diseases drug therapy, Benzodiazepines antagonists & inhibitors, Benzoxazoles pharmacology, Benzoxazoles therapeutic use, Catalepsy drug therapy, Haloperidol antagonists & inhibitors, Intracellular Signaling Peptides and Proteins antagonists & inhibitors, Neuropeptides antagonists & inhibitors, Risperidone antagonists & inhibitors, Urea analogs & derivatives
- Abstract
We have previously shown that the orexin-1 antagonist SB-334867 blocks the electrophysiological effects of haloperidol and olanzapine on the activity of A9 and A10 dopamine neurons. To evaluate if orexin-1 antagonists might block other effects of antipsychotic drugs in animals, we examined the effects of SB-334867 on behavioral, neurochemical, and neuroendocrine effects of antipsychotic drugs. Pretreatment with SB-334867 (0.01-10 mg/kg, intraperitoneal [IP]) significantly decreased the catalepsy produced by the administration of haloperidol (1 mg/kg, subcutaneous [SC]), risperidone (2 mg/kg, SC), and olanzapine (10 mg/kg, SC). Administration of SB-334467 also reversed catalepsy after it had been established in animals pretreated 2 hours earlier with haloperidol. However, pretreatment with SB-334867 (1-10 mg/kg, IP) did not block the decreases in exploratory locomotor activity produced by administration of haloperidol (0.1 mg/kg, SC) or risperidone (0.3 mg/kg, SC). In addition, pretreatment with SB-334867 (1-10 mg/kg, IP) neither blocked the increased levels of dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens or striatum nor the elevation in serum prolactin produced by administration of haloperidol (0.1 mg/kg, SC) and risperidone (1 mg/kg, SC). Administration of SB-334867 alone neither changed locomotor activity and DOPAC or prolactin levels nor produced catalepsy. These results show that orexin-1 antagonists block the catoleptogenic effects of antipsychotics but do not block other locomotor, neurochemical, or neuroendocrine effects of antipsychotics. Because catalepsy is thought to be a good predictor of extrapyramidal symptoms in humans, treatment with orexin-1 antagonists might decrease the occurrence or severity of antipsychotic treatment-emergent extrapyramidal symptoms in humans.
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- 2007
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242. The orexin-1 receptor antagonist SB-334867 blocks the effects of antipsychotics on the activity of A9 and A10 dopamine neurons: implications for antipsychotic therapy.
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Rasmussen K, Hsu MA, and Yang Y
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- Action Potentials drug effects, Analysis of Variance, Animals, Antipsychotic Agents pharmacology, Benzodiazepines pharmacology, Brain cytology, Drug Interactions, Haloperidol pharmacology, Intracellular Signaling Peptides and Proteins pharmacology, Male, Naphthyridines, Neuropeptides pharmacology, Olanzapine, Orexin Receptors, Orexins, Rats, Rats, Sprague-Dawley, Time Factors, Urea pharmacology, Benzoxazoles pharmacology, Dopamine metabolism, Neurons drug effects, Neurons metabolism, Receptors, G-Protein-Coupled antagonists & inhibitors, Receptors, Neuropeptide antagonists & inhibitors, Urea analogs & derivatives
- Abstract
Antipsychotic drugs alter the activity of dopamine neurons in the ventral tegmental area (A10) and substantia nigra pars compacta (A9). As there is a dense projection of orexin neurons from the lateral hypothalamus to A10 dopaminergic neurons, and some antipsychotics have been shown to increase the expression of c-fos in orexin-containing cells in the hypothalamus, we hypothesized that stimulation of orexin receptors plays a role in the effects of antipsychotics on the activity of A9 and A10 dopamine cells. Single-unit recordings in anesthetized rats demonstrated the central effects of the selective orexin-1 receptor antagonist SB-334867 (2 mg/kg, intravenous), as it reversed the excitatory effects of orexin-A administration (6 microg, intracerebroventricular) on the activity of locus coeruleus (LC) cells. Recordings from midbrain dopamine neurons showed that acute administration of SB-334867 alone did not alter the number of spontaneously active A9 or A10 cells, but did reverse: (1) the increase in the number of spontaneously active A9 and/or A10 dopamine cells caused by the acute administration of haloperidol (1 mg/kg, subcutaneous) or olanzapine (10 mg/kg, s.c.) and (2) the decrease in the number of spontaneously active A9 and/or A10 dopamine cells caused by the chronic administration of haloperidol (1 mg/kg/day x 21 days, s.c.) or olanzapine (10 mg/kg/day x 21 days, s.c.). However, SB-334867 did not block a different electrophysiological effect of olanzapine, as it did not block the olanzapine-induced activation of LC cells. These results indicate that activation of orexin-1 receptors plays an important role on the effects of antipsychotic drugs on dopamine neuronal activity and may play an important role in the clinical effects of antipsychotic drugs.
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- 2007
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243. Validation of the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT).
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Armstrong TS, Mendoza T, Gning I, Coco C, Cohen MZ, Eriksen L, Hsu MA, Gilbert MR, and Cleeland C
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Severity of Illness Index, Surveys and Questionnaires, Brain Neoplasms complications, Brain Neoplasms physiopathology
- Abstract
Background: Symptom occurrence has been shown to predict treatment course and survival in patients with solid tumors. Primary brain tumor (PBT) patients are unique in the occurrence of neurologic symptoms. Currently, no instrument exists that measures both neurologic and cancer-related symptoms., Methods: Patients diagnosed with PBT participated in this study. Data was collected at one point in time and included demographic and clinical factors, and the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). The study evaluated the reliability and validity of the MDASI-BT in primary brain tumor patients., Results: Two hundred and one patients participated in this study. Mean symptom severity of items as well as cluster analysis was used to reduce the number of total items to 22 (13 core, 9 brain tumor items). Regression analysis showed more than half (56%) of the variability in symptom severity was explained by brain module items. The MDASI-BT measures six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, generalized symptom, and a gastrointestinal related factor. The internal consistency (reliability) of the instrument was 0.91. The MDASI-BT was sensitive to disease severity based on performance status (P<0.001), tumor recurrence (P<0.01), and mean symptom interference (P<0.001)., Conclusions: The 22 item MDASI-BT demonstrated validity and reliability in patients with PBT. This instrument can be used to identify symptom occurrence throughout the disease trajectory and to evaluate interventions designed for symptom management.
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- 2006
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244. Are chemotherapy patients' HRQoL importance weights consistent with linear scoring rules? A stated-choice approach.
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Johnson FR, Hauber AB, Osoba D, Hsu MA, Coombs J, and Copley-Merriman C
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- Antineoplastic Agents, Linear Models, Neoplasms drug therapy, United States, Drug Therapy, Patient Satisfaction, Quality of Life, Surveys and Questionnaires
- Abstract
Objective: To compare a linear scoring rule with the subjective importance of different domain and symptom levels of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) among patients undergoing chemotherapy., Methods: Using a stated-choice or choice-format conjoint analysis survey instrument, we elicited patient preferences for varying levels of physical, role, social, emotional, and cognitive function along with chemotherapy-related side effects and financial difficulties. A total of 375 patients completed the questionnaire: 159 breast cancer, 117 colorectal cancer, 99 non-small-cell lung cancer; and 21 with unknown tumor type. Constrained maximum likelihood estimates were used to estimate relative importance weights for each level of each domain and symptom., Results: Summary HRQoL measures generally presume that differences among Likert categories are equally important to patients within and across outcomes. Our results indicate strong non-linearities both within and across domain and symptom categories. Improvements from severe pain to mild pain, severe fatigue to no fatigue, and severe social limitations to moderate social limitations are all about twice as important as no work to limited work in the Role domain., Conclusions: Our results indicate large differences in the impact of individual domains and symptoms on patient perceptions of well-being. Most cancer patients are likely to be less concerned about specific symptoms than the impact of those symptoms on their ability to function physically, socially, and in their daily roles.
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- 2006
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245. Stated preferences of patients with cancer for health-related quality-of-life (HRQOL) domains during treatment.
- Author
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Osoba D, Hsu MA, Copley-Merriman C, Coombs J, Johnson FR, Hauber B, Manjunath R, and Pyles A
- Subjects
- Aged, Female, Humans, Male, Middle Aged, United States, Health Status, Neoplasms drug therapy, Patient Satisfaction, Quality of Life, Surveys and Questionnaires
- Abstract
Objectives: It is postulated that patients with different cancer diagnoses, stages of disease and treatments will exhibit different individual preferences for health-related quality-of-life (HRQOL) functional domains and symptoms., Methods: A stated-preference (SP) instrument incorporating all functional domains and symptoms of the EORTC Quality of Life Questionnaire (QLQ-C30) was administered to 400 patients with either breast (n = 150); colorectal (n = 150) or non-small cell lung cancer (n = 100) who had previously experienced chemotherapy. The SP survey asked patients to make choices between a series of hypothetical functional/symptom pairs defined by combinations of HRQOL attributes, and depicted by levels of functioning and symptomatology., Results: In the 400 patients, considered as one group, role, cognitive, and social functioning, fatigue, nausea/vomiting, pain, appetite loss, diarrhea and financial difficulties were most important, whereas physical and emotional functioning, dyspnea, constipation and insomnia were less important. The four effects that patients with breast cancer most wished to avoid were nausea and vomiting, pain, and decreases in emotional and role functioning. Patients with colorectal cancer listed diarrhea as the second most important effect to avoid (after nausea/vomiting, but before pain and role functioning), whereas those with non-small cell lung cancer listed dyspnea as the fourth most important effect to avoid., Conclusion: These results provide more precise information regarding patient treatment concerns than that provided by the usual measurement of HRQOL. This information can be used by clinical trial investigators to design more precise interventions to improve HRQOL in the domains of greatest importance to patients and by all health care professionals to improve counseling of patients.
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- 2006
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246. Development of the cancer therapy satisfaction questionnaire: item generation and content validity testing.
- Author
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Abetz L, Coombs JH, Keininger DL, Earle CC, Wade C, Bury-Maynard D, Copley-Merriman K, and Hsu MA
- Subjects
- Adult, Aged, Europe, Female, Focus Groups, Humans, Interviews as Topic, Male, Middle Aged, Neoplasms psychology, Outcome Assessment, Health Care, Patient Compliance, United States, Antineoplastic Agents therapeutic use, Neoplasms drug therapy, Patient Satisfaction, Surveys and Questionnaires
- Abstract
Objectives: This study was undertaken to develop a new questionnaire, the Cancer Therapy Satisfaction Questionnaire (CTSQ), to focus on the issues oncology patients consider when evaluating chemotherapy in terms of expectations and satisfaction., Methods: Items of the CTSQ were generated through the review of responses from interviews with oncology patients, physicians, and nurses. Analysis of the data was stratified by disease stage, disease type, and country to explore potential differences between these groups. Two rounds of face and content validity testing were then conducted., Results: Patients explained their hopes for efficacy and factors related to treatment satisfaction. Content validity testing in 30 patients, followed by additional testing in 10 patients on oral therapy, suggested that patients felt the questionnaire was clear, comprehensive, relevant, and easy to complete. Minor revisions were implemented to improve clarity, resulting in deletion of 12 items, modification of 17 items and the rewording of "chemotherapy" to "cancer therapy" to ensure patients on oral therapy were able to respond. The CTSQ contains 21 items and assesses seven domains: Expectations of cancer therapy, Feelings about side effects, Oral cancer therapy adherence, Convenience, Satisfaction with cancer therapy, Stopping cancer therapy, and Reasons for nonadherence., Conclusions: The CTSQ was designed for adults with a wide range of cancer types and stages, receiving a variety of cancer treatment formulations. A validation study is currently underway to examine the psychometric properties, further refine the questionnaire and develop scoring methods for the CTSQ.
- Published
- 2005
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247. The economic cost of squamous cell cancer of the head and neck: findings from linked SEER-Medicare data.
- Author
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Lang K, Menzin J, Earle CC, Jacobson J, and Hsu MA
- Subjects
- Aged, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell therapy, Cohort Studies, Combined Modality Therapy, Comorbidity, Female, Head and Neck Neoplasms epidemiology, Head and Neck Neoplasms mortality, Head and Neck Neoplasms therapy, Humans, Male, Medicare, SEER Program, Treatment Outcome, United States epidemiology, Carcinoma, Squamous Cell economics, Head and Neck Neoplasms economics
- Abstract
Objective: To evaluate the excess mortality, resource use, and costs associated with squamous cell carcinoma of the head and neck (SCCHN) among elderly Medicare beneficiaries., Design: Retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and Medicare claims., Subjects: Study cohorts included patients aged 65 years and older who were newly diagnosed as having SCCHN in a SEER registry between 1991 and 1993 (N = 4536) and controls matched 1:1 by age and sex. Patients were followed up for 5 years or until death, whichever occurred first., Results: Initial treatment was primarily surgery and/or radiation among patients with early-stage SCCHN, with only modest use of chemotherapy. Patients with SCCHN had significantly (P<.001) higher 5-year mortality (64% vs 25%) and health care costs than controls. Average Medicare payments (1998 US dollars) among patients with SCCHN were $25 542 higher than those of matched comparison patients (P<.001), with monthly payments 3 times as high ($1428 vs $446). Patients diagnosed as having advanced SCCHN had shorter survival times (5-year mortality, 85%, 75%, 47%, and 35% among patients diagnosed as having distant, regional, local, and in situ cancer, respectively) and higher costs (average total Medicare payments, $53 741, $58 387, $42 698, and $37 434, respectively)., Conclusion: These results suggest that the health economic burden of SCCHN is substantial, with costs that are comparable with or higher than those of other solid tumors.
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- 2004
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248. The selective mGlu2/3 receptor antagonist LY341495 exacerbates behavioral signs of morphine withdrawal and morphine-withdrawal-induced activation of locus coeruleus neurons.
- Author
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Rasmussen K, Hsu MA, and Vandergriff J
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Animals, Locus Coeruleus physiology, Male, Neurons drug effects, Neurons physiology, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate antagonists & inhibitors, Receptors, Metabotropic Glutamate physiology, Amino Acids pharmacology, Excitatory Amino Acid Antagonists pharmacology, Locus Coeruleus drug effects, Morphine Dependence physiopathology, Substance Withdrawal Syndrome physiopathology, Xanthenes pharmacology
- Abstract
Previous research has demonstrated that mGlu2/3 agonists can decrease many behavioral signs and the activation of locus coeruleus (LC) neurons observed during morphine withdrawal. However, it is not known if mGlu2/3 receptors are activated during morphine withdrawal by endogenous glutamate. Therefore, we investigated the effect of a novel metabotropic glutamate 2, 3 (mGlu2/3) receptor antagonist (LY341495) on naltrexone-precipitated behavioral signs of morphine withdrawal and withdrawal-induced activation of LC neurons. Three levels of severity of morphine withdrawal (mild, moderate, and strong) were operationally defined by varying the exposure to morphine. Pretreatment with LY341495 (1 mg/kg, s.c.) had no affect on behavioral signs at the mild level of withdrawal, but significantly increased behavioral signs at the moderate level of withdrawal. At the strong level of withdrawal, 3 and 10 mg/kg, but not 1 mg/kg, LY341495 significantly increased the behavioral signs of withdrawal. In in vivo recordings from anesthetized rats, pretreatment with 1 mg/kg LY341495 did not affect the morphine-withdrawal-induced activation of LC neurons at the mild level of withdrawal. At the moderate level of withdrawal, 1 and 10 mg/kg LY341495 did not affect morphine-withdrawal-induced activation of LC neurons. At the strong level of withdrawal, both 1 and 10 mg/kg LY341495 significantly increased morphine-withdrawal-induced activation of LC neurons. These results indicate that endogenous activation of mGlu2/3 receptors during morphine withdrawal acts to reduce the severity of morphine withdrawal and demonstrates that mGlu2/3 receptors are activated under a physiologically relevant, pathological condition.
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- 2004
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249. Reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale.
- Author
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Marin DB, Flynn S, Mare M, Lantz M, Hsu MA, Laurans M, Paredes M, Shreve T, Zaklad GR, and Mohs RC
- Subjects
- Aged, Dementia classification, Dementia physiopathology, Dementia psychology, Humans, Mental Status Schedule, Observer Variation, Skilled Nursing Facilities, Activities of Daily Living, Cognition, Dementia diagnosis, Geriatric Assessment, Psychiatric Status Rating Scales standards, Severity of Illness Index
- Abstract
Objective: This study investigated the reliability and validity of a chronic care facility adaptation of the Clinical Dementia Rating scale (CDR-CC)., Method: Sixty-two residents in a chronic care facility participated in an inter-rater and 1 month test-retest reliability study. The instrument was validated against the Mini-Mental State Examination (MMSE)., Results: Inter-rater and 1 month test-retest reliability for the global CDR-CC score were excellent (intraclass correlation coefficients 0.99 and 0.92, respectively). The CDR-CC domain and global scores were negatively correlated with the MMSE., Conclusions: The CDR-CC is a global assessment tool that reliably and validly measures cognitive and functional impairment in a chronic care setting., (Copyright 2001 John Wiley & Sons, Ltd.)
- Published
- 2001
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250. The use of the neuropsychiatric inventory in nursing home residents. Characterization and measurement.
- Author
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Wood S, Cummings JL, Hsu MA, Barclay T, Wheatley MV, Yarema KT, and Schnelle JF
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- Adult, Aged, Aged, 80 and over, Caregivers, Female, Humans, Male, Nursing Assistants, Nursing, Practical, Professional Competence standards, Psychiatric Nursing, Reproducibility of Results, Severity of Illness Index, Nursing Homes, Psychiatric Status Rating Scales, Psychomotor Disorders diagnosis
- Abstract
The authors assessed the validity of the nursing home version of the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), comparing the responses of certified nurses' aides (CNAs) and licensed vocational nurses (LVNs) with research observations. Correlations were significant but moderate for all of the domains of the NPI-NH (delusions, hallucinations, agitation/aggression, depression, apathy, disinhibition, euphoria, irritability/lability, and aberrant motor disturbances) except anxiety and appetite disturbance. The LVNs' ratings showed consistently higher correlations with the researchers' behavioral observations than did the CNAs', but were moderate and generally better for residents with high levels of neuropsychiatric symptoms, thus, caution should be used with any untrained rater in the nursing home setting. The NPI-NH used by non-research staff can be useful in identifying residents with significant neuropsychiatric disturbances, but may be limited as an instrument for tracking behavioral changes.
- Published
- 2000
- Full Text
- View/download PDF
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