10 research outputs found
Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis
Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH.
Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6â190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC.
Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal.
Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF
Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis
Background: We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). Patients and Methods: We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18\ua0years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72\ua0months (range 8\u2013182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Results: Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy
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Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks.
Acknowledgements: A.S.P. is supported by the AHA (20SFRN35120123). J.M.R. is supported by the National Institutes of Health (NIH) (K23HL150327). R.V.S. is supported by grants from the American Heart Association (AHA) and NIH. M.N. is supported by NIH (R01HL156975, R01HL131029) and by a Career Investment Award from the Department of Medicine, Boston University School of Medicine. R.E.G. and M.A.S. were funded by R01NR019628. T.T., K.A.W., and L.F. are supported by the National Institute on Agingâs Intramural Research Program. P.R. is supported by the John S. LaDue Memorial Fellowship at Harvard Medical School. Q.S.W. is supported by the NIH (R01HL140074). M.Y.M. was supported by the NIH (K23HL171855). B.C. is supported by an Early Career Investigator Grant from the American Lung Association. The BLSA study was funded by the National Institute on Agingâs Intramural Research Program. Proteomics in CARDIA were funded by a grant to R.K. (R01HL122477). CARDIA is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (75N92023D00002 and 75N92023D00005), Northwestern University (75N92023D00004), University of Minnesota (75N92023D00006) and Kaiser Foundation Research Institute (75N92023D00003). This manuscript has been reviewed by CARDIA for scientific content. Exercise testing in CARDIA was funded by a grant to S.S. and B. Sternfeld (R01HL078972). The Fenland Study is funded by the UK Medical Research Council, with proteomic assessment funded by Somalogic; Investigators T.G., N.J.W. and S.B. received support from the UK Medical Research Council (MC_UU_00006/1, MC_UU_00006/4) as well as the National Institute for Health and Care Research Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The HERITAGE study was supported by several grants from the NHLBI (R01HL45670, R01HL47317, R01HL47321, R01HL47323 and R01HL47327).Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48-0.52) per 1âs.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable
Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis
More is not always better: The impact of value coâcreation fit on B2B and B2C customer satisfaction
Organizations increasingly rely on customer involvement in the value creation process (i.e., co-creation) to enhance customer satisfaction and differentiate themselves from competitors. While past research has largely indicated that more co-creation is beneficial, some have suggested yet not empirically validated that excess co-creation may negatively impact customers. Applying the service-dominant logic, two studies (B2B and B2C customers) offer insight into the appropriate levels of the co-production and value-in-use dimensions of co-creation. For both B2B and B2C customers, polynomial regression and surface plot analyses indicate an inverted U-shaped relationship between value co-creation and satisfaction, establishing that more co-creation is beneficial only up to a point. As such, we inform managers of factors that can cause the relationship between co-creation and satisfaction to peak and then turn negative. Further, customer expertise and process enjoyment moderate this relationship for B2C (but not B2B) customers, thereby offering ways to mitigate the negative effects of excess co-creation for end-customers. The studies also highlight the importance of value co-creation âfitâ between the customer\u27s expected and experienced levels of co-creation. Interestingly, positive misfit (i.e., excess co-creation) retains a stronger negative influence on customer satisfaction than negative misfit (i.e., insufficient co-creation) for both B2B and B2C customers
13Th International Conference On Conservative Management Of Spinal Deformities And First Joint Meeting Of The International Research Society On Spinal Deformities And The Society On Scoliosis Orthopaedic And Rehabilitation Treatment â Sosort-Irssd 2016 Meeting
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