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  1. Weight Gain and Hair Loss during Anti-TNF Therapy

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    Abdo Lutf

    2012-01-01

    Full Text Available Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications were interviewed .Weight gain was observed in 20 patients (13.3% with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3% and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy.

  2. Decreasing trends in hospitalizations during anti-TNF therapy are associated with time to anti-TNF therapy: Results from two referral centres.

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    Mandel, Michael D; Balint, Anita; Golovics, Petra A; Vegh, Zsuzsanna; Mohas, Anna; Szilagyi, Blanka; Szabo, Agnes; Kurti, Zsuzsanna; Kiss, Lajos S; Lovasz, Barbara D; Gecse, Krisztina B; Farkas, Klaudia; Molnar, Tamas; Lakatos, Peter L

    2014-11-01

    Hospitalization is an important outcome measure and a major driver of costs in patients with inflammatory bowel disease. We analysed medical and surgical hospitalization rates and predictors of hospitalization before and during anti-TNF therapy. Data from 194 consecutive patients were analysed retrospectively (males, 45.4%, median age at diagnosis, 24.0 years, infliximab/adalimumab: 144/50) in whom anti-TNF therapy was started after January 1, 2008. Total follow-up was 1874 patient-years and 474 patient-years with anti-TNF exposure. Hospitalization rates hospitalization decreased only in Crohn's disease (odds ratio: 0.59, 95% confidence interval: 0.51-0.70, median 2-years' anti-TNF exposure) with a same trend for surgical interventions (p=0.07), but not in ulcerative colitis. Need for hospitalization decreased in Crohn's disease with early (within 3-years from diagnosis, p=0.016 by McNemar test), but not late anti-TNF exposure. At logistic regression analysis complicated disease behaviour (p=0.03), concomitant azathioprine (p=0.02) use, but not anti-TNF type, gender, perianal disease or previous surgeries were associated with the risk of hospitalization during anti-TNF therapy. Hospitalization rate decreased significantly in patients with Crohn's disease but not ulcerative colitis after the introduction of anti-TNF therapy and was associated with time to therapy. Complicated disease phenotype and concomitant azathioprine use were additional factors defining the risk of hospitalization. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. Effectiveness and Safety of Immunomodulators with Anti-TNF Therapy in Crohn's Disease

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    Osterman, Mark T.; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M.; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R.; Lewis, James D.

    2015-01-01

    Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared using 3 metrics of effectiveness – surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery – and 2 metrics of safety – serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR] 1.20, 95% CI 0.73-1.96), hospitalization (HR 0.82 [0.57-1.19]), discontinuation of anti-TNF therapy or surgery (HR 1.09, [0.88-1.34]), and serious infection (HR 0.93 [0.88-1.34]) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risk of opportunistic infection (HR 2.64 [1.21-5.73]) and herpes zoster (HR 3.16 [1.25-7.97]) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. PMID:25724699

  4. Anti-TNF-alpha therapy for sight threatening uveitis.

    NARCIS (Netherlands)

    E.W. Lindstedt (Eric); G.S. Baarsma (Seerp); R.W.A.M. Kuijpers (Robert); P.M. van Hagen (Martin)

    2005-01-01

    textabstractAIM: To describe the effect of additional treatment with anti-TNF-alpha therapy in a case series of 13 patients with serious sight threatening uveitis. METHODS: 13 patients with serious sight threatening uveitis were included, of whom six had Behcet's disease, five had idiopathic

  5. New Onset of Dermatomyositis/Polymyositis during Anti-TNFTherapies: A Systematic Literature Review

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    Alexandra Maria Giovanna Brunasso

    2014-01-01

    Full Text Available We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM in patients treated with anti-TNFtherapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNFtherapy was recorded. 17 patients were affected by rheumatoid arthritis (RA, one by Crohn’s disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNFtherapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease.

  6. Risk of post-operative complications associated with anti-TNF therapy in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Tauseef Ali; Laura Yun; David T Rubin

    2012-01-01

    There have been increasing concerns regarding the safety of perioperative antitumour necrosis factor (antiTNF) α agents. We performed a literature review to evaluate the postoperative complications associated with perioperative antiTNF use in patients with inflammatory bowel disease. A comprehensive review was performed with a literature search utilizing Pub Med, Cochrane, OVID and EMBASE databases according to published guidelines. To date, there are only data for infliximab. There are three published studies which have assessed postoperative complications with perioperative infliximab use in patients with Crohn's disease (CD), four studies in ulcerative colitis (UC) patients, and one study on both CD and UC patients. Two out of the three studies in CD patients showed no increased postoperative complications associated with perioperative infliximab. Two out of four studies in UC patients also did not show an increase in postoperative complications, and the combined study with CD and UC patients did not show an increased risk as well. Study differences in study designs, patient population and definition of their endpoints. There appears to be a risk of postoperative complications associated with TNF therapy in some patients. Based on these data, careful patient selection and prospective data collection should be performed.

  7. Arterite de Takayasu: tratamento com anti-TNF em uma casuística brasileira Takayasu arteritis: anti-TNF therapy in a Brazilian setting

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    Guilherme Nunes

    2010-06-01

    Full Text Available O objetivo deste estudo é descrever as características clínicas e as respostas às intervenções terapêuticas, incluindo a terapia antifator de necrose tumoral (TNF, em uma série de casos brasileiros de arterite de Takayasu (AT. Foi realizado um estudo observacional, retrospectivo, com base na revisão de prontuários, incluindo todos os pacientes com AT, de acordo com os critérios de classificação do American College of Rheumatology, em acompanhamento no Serviço de Reumatologia do Hospital Universitário da Universidade Federal de Santa Catarina (UFSC, Brasil. Foram incluídos 15 pacientes, sendo 14 (93,3% mulheres, com idade média ao diagnóstico de 29,6 anos. Hipertensão arterial sistêmica (60,0% e ausência de pulsos em membros superiores (53,3% foram os achados clínicos mais comuns ao diagnóstico. As artérias subclávias e carotídeas foram os vasos mais frequentemente acometidos. Doze pacientes (80,0% não obtiveram remissão sustentada em terapia isolada com corticosteroide, tendo sido empregada terapia imunossupressora, sendo metotrexato, azatioprina e ciclofosfamida as drogas utilizadas. Intervenções cirúrgicas foram necessárias em 53,3% dos casos. Três casos (20,0% foram refratários à terapia com corticoides e imunossupressores e foram tratados com agentes anti-TNF, com subsequente remissão da doença. Em conclusão, observou-se que uma parcela importante dos casos de AT é refratária à terapia tradicional e os agentes anti-TNF podem representar uma opção promissora para o controle da doença nesses casos.The aim of this study was to describe clinical features and response to different therapeutic interventions, including anti-tumor necrosis factor (TNF agents, in a case series of Takayasu arteritis (TA from Brazil. A retrospective observational chart-review study was performed including all patients meeting the American College of Rheumatology TA classification criteria followed at the rheumatology

  8. [Anti-TNF-alpha therapy in ulcerative colitis].

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    Lakatos, Péter László; Lakatos, László

    2008-05-18

    The most important factors that determine treatment strategy in ulcerative colitis (UC) are disease extent and severity. Orally-topically administered 5-aminosalicylates (5-ASA) remain the treatment of choice in mild-to-moderate UC. In contrast, the treatment of refractory (to steroids, azathioprine or 5-ASA) and fulminant cases is still demanding. New evidence supports a role for infliximab induction and/or maintenance therapy in these subgroup of patients leading to increased remission and decreased colectomy rates. The aim of this paper is to review the rationale for the use of TNF-alpha inhibitors in the treatment of UC.

  9. Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

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    Francesco Caso

    2014-01-01

    Full Text Available Behçet’s disease (BD is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF- α, interleukin- (IL- 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

  10. Biological treatments in Behçet's disease: beyond anti-TNF therapy.

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    Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

    2014-01-01

    Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

  11. Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects

    DEFF Research Database (Denmark)

    Allez, Matthieu; Karmiris, Konstantinos; Louis, Edouard

    2010-01-01

    The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts....... This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists...

  12. Magnetic resonance enterography changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn’s disease: correlation with SES-CD and clinical-biological markers

    International Nuclear Information System (INIS)

    Stoppino, Luca Pio; Della Valle, Nicola; Rizzi, Stefania; Cleopazzo, Elsa; Centola, Annarita; Iamele, Donatello; Bristogiannis, Christos; Stoppino, Giuseppe; Vinci, Roberta; Macarini, Luca

    2016-01-01

    In recent years, the use of MRI in patients with Crohn’s disease (CD) has increased. However, few data are available on how MRI parameters of active disease change during treatment with anti-TNF and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. The aim of this study was to determine the changes over time in MRI parameters during treatment with anti-TNF in patients with CD, and to verify the correlation between MRI score, endoscopic appearance and clinical-biological markers. We performed a prospective single centre study of 27 patients with active CD (18 males and 9 females; median age of 27,4 ys; age range, 19–49). All patients underwent ileocolonoscopy and MRI at baseline and 26 weeks after anti-TNF therapy. Endoscopic severity was graded according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) was calculated. Patients underwent clinical evaluation (CDAI) and the C-reactive protein (CRP) level was measured. The associations between variables were assessed with Pearson’s bivariate correlation analysis. A total of 135 intestinal segments were studied. The median patient age was 27,4 years, 67 % were male and the mean disease duration was 6,1 years. For induction of remission, 18 patients were treated with infliximab and 9 with adalimumab. The mean SES-CD and MaRIA scores significantly changed at week 26 (SES-CD: 14,7 ± 8,9 at baseline vs. 4,4 ± 4,6 at 26 weeks - p < 0.001; MaRIA: 41,1 ± 14,8 at baseline vs. 32,8 ± 11,7 at 26 weeks - p < 0.001). Also the CDAI and serum levels of CRP decreased significantly following treatment (p < 0.001). The overall MaRIA correlated with endoscopic score and with clinical activity (CDAI) both at baseline and at week 26 (p < 0.05). The correlation between overall MaRIA and CRP was significant only at week 26 (p < 0.001). The MaRIA has a good correlation with SES-CD, a high accuracy for prediction of endoscopic

  13. The Anti-TNFTherapy in the Rheumatoid Arthritis A Terapia Anti-TNF-α na Artrite Reumatóide

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    Lilian Resende Faleiro

    2011-06-01

    Full Text Available Rheumatoid arthritis is a chronic, systemic autoimmune disease of unknown etiology that involves predominantly synovial articulations, which can lead to deformity and destruction. With the progression of the disease, patients with Rheumatoid Arthritis develop inability to perform activities of daily living both as a professional, generating a significant economic impact for the patient and to society. Although the exact cause of rheumatoid arthritis remains unknown, studies conducted over the past two decades has enabled greater understanding of the pathogenesis of this disease. This knowledge has allowed the development of new therapies used to treat severe forms of the disease. The main goal of treatment is to achieve remission, however, when this can not be expected to prevent joint damage and loss of function and even reduce pain. The latest strategies for the treatment of Rheumatoid Arthritis involve the early diagnosis and aggressive control of inflammation. The recognition of pro-inflammatory cytokines expressed more as tumor necrosis factor α (TNF-α and interleukin (IL 1 and IL6 enabled developing new therapies directed against these cytokines targets. TNF-α is a proinflammatory cytokine that plays a key role in immune response, defense against microorganisms and the inflammatory process. Biological agents that inhibit TNF-α are considered effective in reducing activity and in the retardation of structural joint damage in rheumatoid arthritis, especially in forms refractory to conventional treatments. Currently, they are available in Brazil, three anti-TNF-α: infliximab, etanercept and adalimumab. These drugs are relatively safe for Rheumatoid Arthritis, but may, however, present serious infectious complications such as reactivation of latent tuberculosis.The high cost of these drugs, their use in hospital and the risk to opportunistic infections remain the limiting factors for its widespread use in the treatment of Rheumatoid

  14. Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti-TNF therapy

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    Dewbury Keith

    2010-06-01

    Full Text Available Abstract Background Inhibition of tumour necrosis factor (TNF is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA, yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability. Methods Consecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso-phalangeal (MTP joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI. Results 31 patients (24 female, 7 male with RA (12 seronegative, 19 seropositive completed the study: mean age 59.6 (SD 10.1 years, disease duration 11.1 (SD 10.5 years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6. Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar this was not significant. Conclusions Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.

  15. What do we miss? ASAS non-responders on anti-TNF therapy show improvement in performance-based physical function

    NARCIS (Netherlands)

    van Weely, S.F.E.; van Denderen, J.C.; Steultjens, M.P.M.; Nurmohamed, M.T.; Dijkmans, B.A.C.; Dekker, J.; van der Horst-Bruinsma, I.E.

    2013-01-01

    Objective: A prospective study was conducted in order to establish whether AS patients, who are defined as non-responders after 3 months of anti-TNF therapy, show improvement on performance-based tests of physical functioning. Methods: At baseline and 3 months after the start of anti-TNF therapy, AS

  16. Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

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    Nadia E. Aikawa

    Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

  17. Predictors of work disability after start of anti-TNF therapy in a national cohort of Swedish patients with rheumatoid arthritis: does early anti-TNF therapy bring patients back to work?

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    Olofsson, T; Petersson, I F; Eriksson, J K; Englund, M; Nilsson, J A; Geborek, P; Jacobsson, L T H; Askling, J; Neovius, M

    2017-07-01

    To examine predictors of work ability gain and loss after anti-tumour necrosis factor (TNF) start, respectively, in working-age patients with rheumatoid arthritis (RA) with a special focus on disease duration. Patients with RA, aged 19-62 years, starting their first TNF inhibitor 2006-2009 with full work ability (0 sick leave/disability pension days during 3 months before bio-start; n=1048) or no work ability (90 days; n=753) were identified in the Swedish biologics register (Anti-Rheumatic Treatment In Sweden, ARTIS) and sick leave/disability pension days retrieved from the Social Insurance Agency. Outcome was defined as work ability gain ≥50% for patients without work ability at bio-start and work ability loss ≥50% for patients with full work ability, and survival analyses conducted. Baseline predictors including disease duration, age, sex, education level, employment, Health Assessment Questionnaire, Disease Activity Score 28 and relevant comorbidities were estimated using Cox regression. During 3 years after anti-TNF start, the probability of regaining work ability for totally work-disabled patients was 35% for those with disease duration start, disease duration did not predict work ability loss. Baseline disability pension was also a strong predictor of work ability gain after treatment start. A substantial proportion of work-disabled patients with RA who start anti-TNF therapy regain work ability. Those initiating treatment within 5 years of symptom onset have a more than doubled 3-year probability of regaining work ability compared with later treatment starts. This effect seems largely due to the impact of disease duration on disability pension status. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Effect of 1-year anti-TNFtherapy on aortic stiffness, carotid atherosclerosis, and calprotectin in inflammatory arthropathies: a controlled study.

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    Angel, Kristin; Provan, Sella A; Fagerhol, Magne K; Mowinckel, Petter; Kvien, Tore K; Atar, Dan

    2012-06-01

    Premature arterial stiffening and atherosclerosis are increased in patients with inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The proinflammatory protein calprotectin is associated with inflammatory arthropathies, vascular pathology, and acute coronary events. We examined the long-term effects of treatment with tumor necrosis factor (TNF)-α antagonists on aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies, and the relationships to the levels of calprotectin. Fifty-five patients with RA, AS, or PsA and a clinical indication for anti-TNFtherapy were included and followed with regular examinations for 1 year. Thirty-six patients starting with anti-TNFtherapy were compared with a nontreatment group of 19 patients. Examinations included assessments of aortic stiffness (aortic pulse wave velocity, aPWV), CIMT, and plasma calprotectin. After 1 year, aPWV (mean (s.d.)) was improved in the treatment group, but not in the control group (-0.54 [0.79] m/s vs. 0.06 [0.61] m/s, respectively; P = 0.004), and CIMT progression (median (quartile cut-points, 25th and 75th percentiles)) was reduced in the treatment group compared to the control group (-0.002 [-0.038, 0.030] mm vs. 0.030 [0.011, 0.043] mm, respectively; P = 0.01). In multivariable analyses, anti-TNFtherapy over time was associated with improved aPWV (P = 0.02) and reduced CIMT progression (P = 0.04), and calprotectin was longitudinally associated with aPWV (P = 0.02). Long-term anti-TNFtherapy improved aortic stiffness and CIMT progression in patients with inflammatory arthropathies. Calprotectin may be a soluble biomarker reflecting aortic stiffening in these patients.

  19. Anti-TNF-alpha therapy does not modulate leptin in patients with severe rheumatoid arthritis.

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    Gonzalez-Gay, M A; Garcia-Unzueta, M T; Berja, A; Gonzalez-Juanatey, C; Miranda-Filloy, J A; Vazquez-Rodriguez, T R; de Matias, J M; Martin, J; Dessein, P H; Llorca, J

    2009-01-01

    The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA. We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion. There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, pghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48). In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

  20. Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients - baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice

    DEFF Research Database (Denmark)

    Wallman, Johan K; Kapetanovic, Meliha C; Petersson, Ingemar F

    2015-01-01

    , commencing anti-TNF therapy 1999-2011, were followed during three years. Anti-TNF cessation was defined as stopping therapy, without restarting another anti-TNF agent within three months. Differences in the three year developments of patient's visual analogue scale (VAS) scores for global health and pain...

  1. Significant sE-Selectin levels reduction after 6 months of anti-TNFtherapy in non-diabetic patients with moderate-to-severe psoriasis.

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    Genre, Fernanda; Armesto, Susana; Corrales, Alfonso; López-Mejías, Raquel; Remuzgo-Martínez, Sara; Pina, Trinitario; Ubilla, Begoña; Mijares, Verónica; Martín-Varillas, José Luis; Rueda-Gotor, Javier; Portilla, Virginia; Dierssen-Sotos, Trinidad; González-López, Marcos Antonio; González-Vela, María Del Carmen; Blanco, Ricardo; Llorca, Javier; Hernández, José Luis; González-Gay, Miguel Ángel

    2017-12-01

    Psoriasis patients have high risk of atherosclerosis, characterized by endothelial dysfunction. We aimed to study the association of the endothelial activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E-selectin and P-selectin with disease activity and severity in psoriasis patients treated with anti-TNFtherapy. Also, to evaluate the relationship of metabolic syndrome features with these biomarkers and the effect of anti-TNFtherapy on these molecules. Twenty-nine consecutive non-diabetic patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF-α-adalimumab therapy were studied. Metabolic and clinical evaluation was performed prior to anti-TNF-α treatment (time 0) and 6 months later. MCP-1, sE-selectin and sP-selectin serum levels were determined by ELISA. Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the onset of anti-TNFtherapy (p = .05 and .01, respectively). sE-selectin positively correlated with pro-inflammatory molecules such as asymmetric dimethylarginine, sP-selectin and resistin at baseline and month 6 (p psoriasis. Adalimumab therapy led to a reduction in sE-selectin levels, supporting the beneficial effect of anti-TNFtherapy on mechanisms associated with the development of atherosclerosis in psoriasis.

  2. Hypophosphatemic osteomalacia: a case simulating anklylosing spondylitis treated with anti-TNF therapy.

    Science.gov (United States)

    Sivas, F; Yurdakul, F G; Durak, M; Hatipoğlu, G; Önal, E D; Bodur, H

    2016-12-01

    In this case, a young male patient diagnosed as hypophosphatemic osteomalacia and ankylosing spondylitis (AS) will be assessed by literature. A 32-year-old male patient who had been previously diagnosed as ankylosing spondylitis and hypophosphatemic osteomalacia was admitted to our clinic. In the beginning of the disease, he complained of pain on the first metatarsal bone and low back. Sacroiliac magnetic resonance (MR) images were interpreted as sacroiliitis. He was diagnosed as AS, and referred to many hospitals and received several therapies. He did not benefit from the treatment and his complaints worsened. The human leukocyte antigen (HLA) B-27 test was negative and alkaline phosphatase level was high. Old femur fractures were reported in the whole body bone scintigraphy. In addition, the patient was diagnosed with osteomalacia. While the patient was receiving vitamin D, oral phosphate, anti-tumor necrosis factor therapy was added. Patient's diagnosis was reevaluated. His final diagnosis was hypophosphatemic osteomalacia instead of ankylosing spondylitis.

  3. Accuracy of Consecutive Fecal Calprotectin Measurements to Predict Relapse in Inflammatory Bowel Disease Patients Under Maintenance With Anti-TNF Therapy: A Prospective Longitudinal Cohort Study.

    Science.gov (United States)

    Ferreiro-Iglesias, Rocio; Barreiro-de Acosta, Manuel; Lorenzo-Gonzalez, Aurelio; Dominguez-Muñoz, Juan E

    2018-03-01

    Predicting relapse in inflammatory bowel disease (IBD) patients could allow early changes in therapy. We aimed at evaluating the accuracy of consecutive fecal calprotectin (FC) measurements to predict flares in IBD patients under maintenance treatment with anti-tumor necrosis factor (TNF) drugs. A prospective longitudinal cohort study with 16-month follow-up period was designed. IBD patients in clinical remission for at least 6 months under anti-TNF therapy were included. FC was quantified at 4-month intervals for 1 year, and patients were clinically evaluated for relapse at 2-month intervals. Diagnostic accuracy of FC for predicting relapse was evaluated by receiver-operating characteristic curve analysis. In total, 95 of 106 included patients finalized the study and were analyzed (median age 44 y, 50.5% female, 75% with Crohn's disease). A total of 30 patients (31.6%) had a relapse over follow-up. FC concentration was significantly higher in patients who relapsed (477 μg/g) than in patients who maintained in remission (65 μg/g) (Ppredict remission was 130 μg/g (negative predictive value of 100%), and 300 μg/g to predict relapse (positive predictive value of 78.3%). FC is a good predictor of clinical relapse and a particularly good predictor of remission over the following 4 months in patients with IBD on maintenance therapy with anti-TNF drugs. FC levels 300 μg/g allow predicting relapse with a high probability at any time over the following 4 months.

  4. Two-year survival rates of anti-TNFtherapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA.

    Science.gov (United States)

    Iannone, F; Lopriore, S; Bucci, R; Scioscia, C; Anelli, M G; Notarnicola, A; Lapadula, G

    2015-05-01

    To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.

  5. Anti-TNF-α biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2012-01-01

    This article discusses the rationale behind recommending immunopharmacological guidance of long-term therapies with genetically engineered anti-TNF-α immunoglobulin constructs. Arguments why therapeutic decision-making should not rely on clinical outcome alone are presented. Central...... to this is that the use of theranostics (i.e., monitoring circulating levels of functional anti-TNF-α drugs and antidrug antibodies) would markedly improve treatment because therapies can be tailored to individual patients and provide more effective and economical long-term therapies with minimal risk of side effects....... Large-scale immunopharmacological knowledge of how patients 'handle' TNF-α biopharmaceuticals would also help industry develop more effective and safer TNF-α inhibitors....

  6. Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

    Science.gov (United States)

    Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

    2014-01-01

    Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds. PMID:24711694

  7. Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis.

    Science.gov (United States)

    Semeraro, Francesco; Arcidiacono, Barbara; Nascimbeni, Giuseppe; Angi, Martina; Parolini, Barbara; Costagliola, Ciro

    2014-01-01

    Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.

  8. Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

    Directory of Open Access Journals (Sweden)

    Semeraro F

    2014-03-01

    Full Text Available Francesco Semeraro,1 Barbara Arcidiacono,2 Giuseppe Nascimbeni,1 Martina Angi,1 Barbara Parolini,2 Ciro Costagliola31Eye Clinic, Department of Neurological Sciences and Vision, University of Brescia, Brescia, Italy; 2Department of Ophthalmology, S. Anna Hospital, Brescia, Italy; 3Eye Clinic, Department of Health Sciences, University of Molise, Campobasso, ItalyAbstract: Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.Keywords: adalimumab, etanercept, infliximab

  9. NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

    Science.gov (United States)

    Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

    2016-03-01

    Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

  10. Anti-TNF therapy for paediatric IBD: the Scottish national experience.

    Science.gov (United States)

    Cameron, F L; Wilson, M L; Basheer, N; Jamison, A; McGrogan, P; Bisset, W M; Gillett, P M; Russell, R K; Wilson, D C

    2015-04-01

    Biological agents are being increasingly used in the UK for paediatric-onset inflammatory bowel disease (PIBD) despite limited evidence and safety concerns. We evaluated effectiveness and safety in the clinical setting, highlighting drug cost pressures, using our national Scottish PIBD biological registry. Complete usage of the biological agents, infliximab (IFX) and adalimumab (ADA) for treatment of PIBD (in those aged Scottish Paediatric Gastroenterology, Hepatology and Nutrition (PGHAN) national managed service network (all regional PGHAN centres and paediatric units within their associated district general hospitals). 132 children had biological therapy; 24 required both agents; 114 had Crohn's disease (CD), 16 had ulcerative colitis (UC) and 2 had IBD Unclassified (IBDU). 127 children received IFX to induce remission; 61 entered remission, 49 had partial response and 17 had no response. 72 were given maintenance IFX and 23 required dose escalation. 18 had infusion reactions and 27 had adverse events (infections/other adverse events). 29 had ADA to induce remission (28 CD and 1 UC), 24 after IFX; 10 entered remission, 12 had partial response and 7 had no response. All had maintenance; 19 required dose escalation. 12 children overall required hospitalisation due to drug toxicity. No deaths occurred with either IFX or ADA. Complete accrual of the Scottish nationwide 'real-life' experience demonstrates moderate effectiveness of anti tumour necrosis factor agents in severe PIBD but duration of effect is limited; significant financial issues (drug cost-need for dose escalation and/or multiple biological usage) and safety issues exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden.

    Science.gov (United States)

    Wallman, Johan K; Jöud, Anna; Olofsson, Tor; Jacobsson, Lennart T H; Bliddal, Henning; Kristensen, Lars E

    2017-05-01

    The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  12. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Gregory, Adam P; Dendrou, Calliope A; Attfield, Kathrine E

    2012-01-01

    ), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further...... make to disease risk has raised questions regarding their medical relevance. Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS...... substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases...

  13. Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy

    DEFF Research Database (Denmark)

    Wallman, Johan K; Jöud, Anna; Olofsson, Tor

    2017-01-01

    Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before...

  14. Monitoring Crohn's disease during anti-TNFtherapy: validation of the magnetic resonance enterography global score (MEGS) against a combined clinical reference standard

    International Nuclear Information System (INIS)

    Prezzi, Davide; Bhatnagar, Gauraang; Makanyanga, Jesica; Halligan, Steve; Taylor, Stuart Andrew; Vega, Roser

    2016-01-01

    To assess the ability of magnetic resonance enterography global score (MEGS) to characterise Crohn's disease (CD) response to anti-TNFtherapy. Thirty-six CD patients (median age 26 years, 20 males) commencing anti-TNFtherapy with concomitant baseline MRI enterography (MRE) were identified retrospectively. Patients' clinical course was followed and correlated with subsequent MREs. Scan order was randomised and MEGS (a global activity score) was applied by two blinded radiologists. A physician's global assessment of the disease activity (remission, mild, moderate or severe) at the time of MRE was assigned. The cohort was divided into clinical responders and non-responders and MEGS compared according to activity status and treatment response. Interobserver agreement was assessed. Median MEGS decreased significantly between baseline and first follow-up in responders (28 versus 6, P < 0.001) but was unchanged in non-responders (26 versus 18, P = 0.28). The median MEGS was significantly lower in clinical remission (9) than in moderate (14) or severe (29) activity (P < 0.001). MEGS correlated significantly with clinical activity (r = 0.53; P < 0.001). Interobserver Bland-Altman limits of agreement (BA LoA) were -19.7 to 18.5. MEGS decreases significantly in clinical responders to anti-TNFtherapy but not in non-responders, demonstrates good interobserver agreement and moderate correlation with clinical disease activity. (orig.)

  15. Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    2014-01-01

    Full Text Available Objective. TRAIL is a potential biomarker of cardiovascular (CV disease. Ankylosing spondylitis (AS is a chronic inflammatory disease associated with metabolic syndrome (MeS and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNFtherapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

  16. Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review.

    Science.gov (United States)

    Martelli, Laura; Olivera, Pablo; Roblin, Xavier; Attar, Alain; Peyrin-Biroulet, Laurent

    2017-01-01

    Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.

  17. Patients receiving anti-TNF therapies experience clinically important improvements in RA-related fatigue: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

    Science.gov (United States)

    Druce, Katie L; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

    2015-06-01

    Pro-inflammatory cytokines such as TNF-α are important in the pathogenesis of fatigue in conditions such as RA. This study aimed to determine whether fatigue improved in a cohort of RA patients with clinically relevant fatigue commencing anti-TNFtherapy and, if so, to identify predictors of improvement. Participants recruited to a long-term observational cohort study (the British Society for Rheumatology Biologics Register for RA) provided information on fatigue using the 36-item Short Form Health Survey (SF-36) vitality subscale. The prevalence of severe baseline fatigue (SF-36 vitality ≤12.5) was calculated and improvements, considered as (i) absolute values and (ii) improvement from severe to non-severe fatigue (SF-36 vitality >12.5), were examined 6 months subsequently. A comprehensive set of putative predictors of fatigue improvement were evaluated using multivariable logistic regression. In 6835 participants the prevalence of severe baseline fatigue was 38.8%. Of those with severe fatigue, 70% reported clinically relevant improvement and 66% moved to the non-severe fatigue category (i.e. improvers). The mean change for improvers was three times the minimum clinically important difference for improvement (33.0 U). Independent baseline predictors of improvement were female sex [odds ratio (OR) 1.3 (95% CI 1.1, 1.7)], not being unemployed due to ill health [OR 1.5 (95% CI 1.2, 1.7)], low disability [OR 1.2 (95% CI 1.001, 1.5)], seropositivity [OR 1.2 (95% CI 0.98, 1.4)], not using steroids [OR 1.2 (95% CI 1.03, 1.5)], no history of hypertension [OR 1.4 (95% CI 1.1, 1.6)] or depression [OR 1.3 (95% CI 1.1, 1.5)] and good mental health [SF-36 mental health subscale >35; OR 1.4 (95% CI 1.2, 1.7)]. Fatigued RA patients reported substantial improvement in their fatigue after commencing anti-TNFtherapy. Further, a number of clinical and psychosocial baseline factors identified those most likely to improve, supporting future stratified approaches to RA

  18. Off-Label Uses of Anti-TNF Therapy in Three Frequent Disorders: Behçet’s Disease, Sarcoidosis, and Noninfectious Uveitis

    Directory of Open Access Journals (Sweden)

    Daniel Sánchez-Cano

    2013-01-01

    Full Text Available Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet’s disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.

  19. Anti-TNFtherapy in patients with refractory uveitis due to Behçet's disease: a 1-year follow-up study of 124 patients.

    Science.gov (United States)

    Calvo-Río, Vanesa; Blanco, Ricardo; Beltrán, Emma; Sánchez-Bursón, Juán; Mesquida, Marina; Adán, Alfredo; Hernandez, María Victoria; Hernandez Garfella, Marisa; Valls Pascual, Elia; Martínez-Costa, Lucía; Sellas-Fernández, Agustí; Cordero Coma, Miguel; Díaz-Llopis, Manuel; Gallego, Roberto; Salom, David; García Serrano, José L; Ortego, Norberto; Herreras, José M; Fonollosa, Alejandro; García-Aparicio, Angel M; Maíz, Olga; Blanco, Ana; Torre, Ignacio; Fernández-Espartero, Cruz; Jovani, Vega; Peiteado-Lopez, Diana; Pato, Esperanza; Cruz, Juan; Fernández-Cid, Carlos; Aurrecoechea, Elena; García, Miriam; Caracuel, Miguel A; Montilla, Carlos; Atanes, Antonio; Hernandez, Félix Francisco; Insua, Santos; González-Suárez, Senén; Sánchez-Andrade, Amalia; Gamero, Fernando; Linares, Luis; Romero-Bueno, Fredeswinda; García, A Javier; Almodovar, Raquel; Minguez, Enrique; Carrasco Cubero, Carmen; Olive, Alejandro; Vázquez, Julio; Ruiz Moreno, Oscar; Jiménez-Zorzo, Fernando; Manero, Javier; Muñoz Fernández, Santiago; Rueda-Gotor, Javier; González-Gay, Miguel A

    2014-12-01

    The aim of this study was to assess the efficacy of anti-TNFtherapy in refractory uveitis due to Behçet's disease (BD). We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNFtherapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 μm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 μm) that improved from 420 μm (s.d. 119.5) at baseline to 271 μm (s.d. 45.6) at month 12 (P uveitis. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    Directory of Open Access Journals (Sweden)

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs versus DMARDs alone for ankylosing spondylitis (AS with reduced pulmonary function vital capacity (FVC%. Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT, Borg scale after 6MWT, and St. George’s Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P=0.04. Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5% in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55% in the DMARDs group (P=0.04. Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

  1. Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    2017-03-01

    Full Text Available We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD, to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51. A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively. In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.

  2. Comparative Efficacy and Acceptability of Anti-TNF-Alpha Therapy in Ankylosing Spondylitis: A Mixed-Treatments Comparison

    Directory of Open Access Journals (Sweden)

    Yehua Wang

    2016-09-01

    Full Text Available Background: Tumor necrosis factor α (TNFα antagonists, namely, golimumab, adalimumab, infliximab, etanercept and certolizumab have been prescribed to alleviate and treat ankylosing spondylitis (AS. However, the lack of comparative evidence does not enable us to make constructive recommendations particularly for AS patient populations. Methods: Eligible controlled trials regarding the above 5 anti-TNFα therapies were searched electronically through PubMed, Embase and Cochrane until April 1, 2015. Odds ratios (ORs were estimated and compared for efficacy (ASAS20, ASAS40, ASAS5/6 responses and ASAS partial remission and acceptability (serious adverse effects (SAE among the anti-TNFα reagents. Results: Totally, 25 trials with 2989 participants were incorporated in this mixed treatment comparison. All the 5 TNFα blockers achieved better ASAS20, ASAS40, ASAS5/6 and ASAS-PR responses than the placebo. Furthermore, there was no significant distinction existed among inter-drug comparisons, except that unfavorable effects induced by certolizumab seemed to be less severe than those by etanercept (OR = 0.22, 95% CI: 0.05-0.93. Apart from that, etanercept was estimated to arrive at the most favorable ASAS20 response (90.6% and SAE (83.6%, while infliximab seemed to accomplish the best ASAS40 (83.6% and ASAS-PR responses (77.3%. In addition, adalimumab was estimated to rank the highest ASAS5/6 response (75.0%. Conclusions: Etanercept, infliximab and adalimumab might be prioritized among the commonly recognized 5 anti-TNFα therapies specific for AS patients, though existing evidence did not suffice to confirm significant superiority among the above 5 anti-TNFα reagent.

  3. Sick leave in patients with ankylosing spondylitis before and after anti-TNF therapy: a population-based cohort study.

    Science.gov (United States)

    Kristensen, Lars E; Petersson, Ingemar F; Geborek, Pierre; Jöud, Anna; Saxne, Tore; Jacobsson, Lennart T H; Englund, Martin

    2012-02-01

    To study levels of sick leave and disability pension before and after TNF-antagonist therapy in AS patients. Using the population-based South Swedish Arthritis Treatment Group register, we identified 139 AS patients (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on sick leave in 30-day intervals from 12 months before treatment start until 12 months after. For each AS patient, we randomly selected four subjects from the general population matched for age, sex and area of residence. One to 3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment start, this fraction dropped to 15%, and further declined to 12% at 12 months (P patients with the general population, the relative risk of being on sick leave 3 months before treatment, treatment start and 12 months after treatment start was 8.0 (95% CI 4.6, 13.9), 9.2 (95% CI 5.4, 15.7) and 4.0 (95% CI 2.1, 6.3), respectively. The decrease in sick leave was not substantially offset by changes in disability pension. There is a decline in sick leave during the first 12 months after initiation of TNF-antagonist treatment in AS patients not explained by societal factors or secular trends. The proportion of AS patients on disability pension remained unchanged during the observation period.

  4. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    % of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use...... article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies....

  5. Most patients who reach disease remission following anti-TNF therapy continue to report fatigue: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

    Science.gov (United States)

    Druce, Katie L; Bhattacharya, Yagnaseni; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

    2016-10-01

    RA-related fatigue is common and debilitating, but does not always respond to immunotherapy. In the context of anti-TNF therapy, we aimed to examine whether patients achieving disease remission experienced remission of fatigue. Data from the British Society for Rheumatology Biologics Register for RA were used. In participants with severe baseline fatigue [36-item Short Form Health Survey (SF-36) vitality score ⩽12.5], we identified those in disease remission [28-joint DAS (DAS28) 12.5) and complete remission (SF-36 vitality score >50) at follow-up. Demographic (e.g. sex, age), clinical (e.g. inflammation, joint erosion and co-morbidities) and psychosocial (e.g. SF-36 domains and HAQ) characteristics were compared between responder and non-responder groups. Severe baseline fatigue was reported by 2652 participants, of whom 271 (10%) achieved a DAS28 <2.6 by 6 months. In total, 225 participants (83%) reported partial remission and were distinguished from those who did not by better health status on all psychosocial domains. Far fewer [n = 101 (37.3%)] reported full fatigue remission. In addition to reporting clinically poorer health status, they were distinguished on the basis of a history of hypertension, depression and stroke as well as baseline treatment use of steroids and antidepressants. Despite achieving clinical remission, many RA patients do not achieve complete remission of their fatigue. Therefore, despite being important in overall disease control, reductions in disease activity are not always sufficient to ameliorate fatigue, so other symptom-specific management approaches must be considered for those for whom fatigue does not resolve. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue.

    Directory of Open Access Journals (Sweden)

    Simeone Marino

    2007-10-01

    Full Text Available The immune response to Mycobacterium tuberculosis (Mtb infection is complex. Experimental evidence has revealed that tumor necrosis factor (TNF plays a major role in host defense against Mtb in both active and latent phases of infection. TNF-neutralizing drugs used to treat inflammatory disorders have been reported to increase the risk of tuberculosis (TB, in accordance with animal studies. The present study takes a computational approach toward characterizing the role of TNF in protection against the tubercle bacillus in both active and latent infection. We extend our previous mathematical models to investigate the roles and production of soluble (sTNF and transmembrane TNF (tmTNF. We analyze effects of anti-TNF therapy in virtual clinical trials (VCTs by simulating two of the most commonly used therapies, anti-TNF antibody and TNF receptor fusion, predicting mechanisms that explain observed differences in TB reactivation rates. The major findings from this study are that bioavailability of TNF following anti-TNF therapy is the primary factor for causing reactivation of latent infection and that sTNF--even at very low levels--is essential for control of infection. Using a mathematical model, it is possible to distinguish mechanisms of action of the anti-TNF treatments and gain insights into the role of TNF in TB control and pathology. Our study suggests that a TNF-modulating agent could be developed that could balance the requirement for reduction of inflammation with the necessity to maintain resistance to infection and microbial diseases. Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary TB if used in areas where exposure is likely.

  7. Improvement of Anti-TNF-α Antibody-Induced Palmoplantar Pustular Psoriasis Using a 308-nm Excimer Light

    Directory of Open Access Journals (Sweden)

    Natsuko Iga

    2012-11-01

    Full Text Available Anti-tumor necrosis factor (TNF-α antibody is utilized in the treatment of a variety of chronic inflammatory conditions, including psoriasis. However, it can induce paradoxical development and/or exacerbation of psoriasis in the course of anti-TNF-α antibody treatment, which is sometimes refractory to conventional treatments. Herein, we report a case of refractory palmoplantar pustular psoriasis induced by anti-TNF-α antibody treatment, which was improved by treatment with a 308-nm excimer light. The 308-nm excimer light has less long-term risks than narrow-band UVB. The 308-nm excimer light may be a good therapeutic option for refractory psoriatic skin lesions induced by anti-TNF-α antibody therapy because of localized side effects without systemic problems, short length of treatment and low cumulative dosages of UV light.

  8. Biological anti-TNF drugs

    DEFF Research Database (Denmark)

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-01-01

    practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure...... is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological...

  9. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

    NARCIS (Netherlands)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2010-01-01

    OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

  10. Changing face of care for patients with moderate to severe inflammatory bowel disease: the role of specialist nurses in the governance of anti-TNF prescribing.

    Science.gov (United States)

    Connell, W R; Samyue, T; Gibson, P R; Lachal, S; Moore, G T; Macrae, F A; Van Langenberg, D R

    2015-11-01

    Anti-tumour necrosis factor (TNF) therapy is highly effective for inflammatory bowel disease (IBD), but expensive and potentially toxic. Meticulous supervision prior to and during anti-TNF treatment is required to screen and monitor patients for adverse clinical events. In addition, a systematic administrative process is necessary to comply with Australian Medicare requirements and ensure ongoing therapy is uninterrupted. IBD nurses are essential components of multidisciplinary IBD services, but their role in facilitating the safe and timely delivery of anti-TNF drugs is unacknowledged. The aim of the study was to calculate time spent by IBD nurses on anti-TNF drug governance and its indirect cost. Time spent on activities related to anti-TNF governance was retrospectively assessed by questionnaire among IBD nurses employed at Melbourne hospitals. The capacity of IBD clinics at these hospitals was separately evaluated by surveying medical heads of clinics. On average, each Melbourne IBD service handled 150 existing and 40 new anti-TNF referrals in 2013. The average annual time spent by nurses supervising an existing and newly referred anti-TNF patient was 3.5 and 5.25 h respectively, or a minimum of two full working days per week. If clinicians undertook this activity during normal clinic time, the organisational opportunity cost was at least 58%. Anti-TNF therapy governance is an essential quality component of IBD care that is associated with a definite, indirect cost for every patient treated. IBD nurses are best positioned to undertake this role, but an activity-based funding model is urgently required to resource this element of their work. © 2015 Royal Australasian College of Physicians.

  11. Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

    Science.gov (United States)

    Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

    2015-07-01

    The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

    Science.gov (United States)

    Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

    2017-07-01

    To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68 + , CD20 + , CD3 + cells and CD31 + vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68 + , CD20 + , CD3 + , CD31 + cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68 + (p=0.02) and CD3 + cells (p=0.04) as well as CD31 + vessels (p<0.001) than PDUS-negative patients with RA in remission. PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. Published by the BMJ

  13. Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet's disease.

    Science.gov (United States)

    Iwata, Shigeru; Saito, Kazuyoshi; Yamaoka, Kunihiro; Tsujimura, Shizuyo; Nawata, Masao; Hanami, Kentaro; Tanaka, Yoshiya

    2011-04-01

    It is often difficult to manage refractory gastrointestinal tract complications of Behçet's disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3-5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.

  14. Potential impact of diet on treatment effect from anti-TNF drugs in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

    2017-01-01

    We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies...... for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had......% CI: 1.73–4.31, p diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

  15. Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

    2017-01-01

    We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest...... inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies......% CI: 1.73-4.31, p impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

  16. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Brynskov, Jørn; Thomsen, Ole Østergaard

    2014-01-01

    OBJECTIVE: Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn's disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons...... by response rates, was similar: 58% and 53%, respectively, p=0.81; difference 5% (-19% to 28%). For per-protocol patients, treatment costs were even lower (56%) in the algorithm-treated group (€ 4062 vs € 9178, presponse rates (47% vs 53%, p=0.78; difference -5% (-33% to 22...

  17. [Anti-TNF alpha in dermatology].

    Science.gov (United States)

    Mahe, E; Descamps, V

    2002-12-01

    The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

  18. B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocytes: A Review of the Literature.

    Science.gov (United States)

    Pala, Ozlem; Diaz, Alain; Blomberg, Bonnie B; Frasca, Daniela

    2018-05-22

    The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines. A PubMed search was conducted to review recent advances related to B lymphocytes and the effects of anti-TNF-α on B lymphocytes in rheumatoid arthritis. B lymphocytes play an important role in the pathogenesis of rheumatoid arthritis. In this review, we summarize the major mechanisms by which B lymphocytes play a pathologic role in the development and propagation of the disease, as B lymphocytes are recruited to the synovial fluid, where they contribute to local inflammation through the secretion of pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) and present antigens to T cells. We discuss the effects of TNF-α, either direct or indirect, on B lymphocytes expressing receptors for this cytokine. We also show that total B-cell numbers have been reported to be reduced in the blood of patients with rheumatoid arthritis versus healthy controls, but are significantly increased up to normal levels in patients undergoing anti-TNFtherapy. As for B-cell subsets, controversial results have been reported, with studies showing decreased frequencies of total memory B cells (and memory subsets) and others showing no differences in patients versus healthy controls. Studies investigating the effects of anti-TNFtherapy have also given controversial results, with therapy found to increase (or not) the frequency of memory B lymphocytes, in patients with rheumatoid arthritis versus healthy controls. Those highly variable results could have been due to differences in patient characteristics and limited numbers of subjects. Finally, we summarize the effects of blocking TNF-α with anti-TNF-α agents on possible infections that patients with rheumatoid arthritis may contract, as well as on

  19. The Relevance of Vitamin D and Antinuclear Antibodies in Patients with Inflammatory Bowel Disease Under Anti-TNF Treatment: A Prospective Study.

    Science.gov (United States)

    Santos-Antunes, João; Nunes, Amadeu Corte-Real; Lopes, Susana; Macedo, Guilherme

    2016-05-01

    The importance of vitamin D in inflammatory bowel disease (IBD) has been analyzed in former studies, namely concerning the severity of the disease and the efficacy of anti-tumor necrosis factor (TNF) medications. In several inflammatory conditions, biologics have been associated with an autoimmune response with formation of antinuclear antibodies (ANA). In addition, an inverse relationship between vitamin D levels and ANA has been documented. We aimed to evaluate the clinical importance of the link between vitamin D, ANA, and anti-TNF in patients with IBD. Prospective study including patients with IBD with indication to start anti-TNF, between 2009 and 2014. Deficiency and extreme deficiency of vitamin D were defined as levels of 25-hydroxyvitamin D below 20 and 4 ng/mL, respectively. ANA titers were considered positive if higher or equal to 1/100. Among 68 patients (56 with Crohn's Disease, 12 with ulcerative colitis), vitamin D deficiency was detected in 93%. Pretreatment positivity for ANA was related to higher failure rates of anti-TNF treatment (P = 0.008). Pretreatment positivity for ANA and extreme vitamin D deficiency were significant risk factors for adverse events associated with anti-TNF therapy. A significant link was found between extreme deficiency of vitamin D and the presence of ANA. Our study highlights the association between vitamin D deficiency and pretreatment positivity for ANA with the risk for anti-TNF failure and adverse events, and the inverse relationship between vitamin D levels and ANA. Due to the high prevalence of vitamin D deficiency in IBD and the immune-mediated nature of the disease, these elements should be evaluated before starting biologics.

  20. Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Sode, Jacob; Vogel, Ulla; Bank, Steffen

    2015-01-01

    : In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value... and European League Against Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for multiple testing (q-value) and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF) status. RESULTS: Six of twenty successfully genotyped...

  1. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    Immunogenicity of biopharmaceuticals is complex and influenced by both structural and pharmacological factors, and by patient-related conditions such as disease being treated, previous and concomitant therapies, and individual immune responsiveness. Essential for tailored therapeutic strategies b...

  2. Birth Outcomes in Children Fathered by Men Treated with Anti-TNF-α Agents Before Conception

    DEFF Research Database (Denmark)

    Larsen, Michael Due; Friedman, Sonia; Magnussen, Bjarne

    2016-01-01

    OBJECTIVES: The safety of paternal use of anti-tumor necrosis factor-α (TNF-α) agents immediately prior to conception is practically unknown. On the basis of nationwide data from Danish health registries, we examined the association between paternal use of anti-TNF-α agents within 3 months before...... the safety of paternal preconceptional use of anti-TNF-α agents. The result regarding SGA should, however, be interpreted with caution as we found an increased risk, although not significantly increased....

  3. T-helper immune phenotype may underlie 'paradoxical' tumour necrosis factor-α inhibitor therapy-related psoriasiform dermatitis.

    Science.gov (United States)

    Moy, A P; Murali, M; Kroshinsky, D; Horn, T D; Nazarian, R M

    2018-01-01

    Therapeutics targeting tumour necrosis factor (TNF)-α are effective for psoriasis; however, in patients treated for other disorders, psoriasis may worsen and psoriasiform dermatitis (PsoD) may arise. T helper (Th) cytokines in psoriasis upregulate keratin (K)17, which modulates TNF-α transduction, leading to vascular adhesion molecule upregulation and lymphocytic extravasation. We investigated Th phenotype and expression of K17, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in psoriasis and anti-TNF-α-related PsoD. Skin biopsies from patients with psoriasis unresponsive to TNF-α inhibitor therapy (n = 11), PsoD-related to TNF-α inhibition (n = 9), untreated psoriasis (n = 9) or atopic dermatitis (AD; n = 9) were immunohistochemically analysed for Th1, Th2, Th17 and Th22. Expression of K17, ICAM-1 and VCAM-1 was also examined. Anti-TNF-α-unresponsive psoriasis and anti-TNF-α-related PsoD showed decreased Th1 : Th2 raio and increased Th17 : Th1 ratio compared with untreated psoriasis. Anti-TNF-α-unresponsive psoriasis had significantly fewer Th1 (4% vs. 12%) and more Th17 (51% vs. 20%) cells than untreated psoriasis. No difference in Th22 cells was identified. K17 was present in all cases of untreated psoriasis and anti-TNF-α-related PsoD, 91% of anti-TNF-α-unresponsive psoriasis, and only 22% of AD. VCAM-1 and ICAM-1 in anti-TNF-α-related PsoD was akin to untreated psoriasis, but decreased in anti-TNF-α-unresponsive psoriasis. These findings further the current understanding of the anti-TNF-α-related psoriasiform phenotype and support a rationale for therapeutic targeting of interleukin-17 and TNF-α in combination. © 2017 British Association of Dermatologists.

  4. Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study

    DEFF Research Database (Denmark)

    Nørgård, B M; Nielsen, J; Qvist, N

    2012-01-01

    It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC).......It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC)....

  5. Can We Predict the Efficacy of Anti-TNF-α Agents?

    Science.gov (United States)

    Lopetuso, Loris Riccardo; Gerardi, Viviana; Papa, Valerio; Scaldaferri, Franco; Rapaccini, Gian Lodovico; Gasbarrini, Antonio; Papa, Alfredo

    2017-09-14

    The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients. Thus, the identification of predicting factors of efficacy is crucial to allow clinicians to efficiently use these therapies, avoiding them when they are ineffective and eventually shifting towards alternative biological therapies with the end goal of optimizing the cost-effectiveness ratio. In this review, we aim to identify the predictive factors of short- and long-term benefits of anti-TNFtherapy in IBD patients. In particular, multiple patient-, disease- and treatment-related factors have been evaluated.

  6. Pre-operative use of anti-TNF-alpha agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz; Nielsen, J.; Qvist, N.

    2013-01-01

    BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-alpha) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-alpha agents on post-operative outcomes 30 and 6...

  7. Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Jacob Sode

    Full Text Available To determine whether genetic variation within genes related to the Toll-like receptor, inflammasome and interferon-γ pathways contributes to the differences in treatment response to tumour necrosis factor inhibitors (anti-TNF in patients with rheumatoid arthritis (RA.In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value<0.05 between genotypes and European League Against Rheumatism (EULAR treatment responses. False Discovery Rate corrections for multiple testing (q-value and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF status.Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response. TLR5(rs5744174 variant allele carriers (odds ratio(OR = 1.7(1.1-2.5,p = 0.010,q = 0.46 and TLR1(rs4833095 homozygous variant carriers (OR = 2.8(1.1-7.4,p = 0.037,q = 0.46 had higher odds for a positive treatment response. NLRP3(rs10754558 variant allele carriers (odds ratio(OR = 0.6(0.4-1.0,p = 0.045,q = 0.46 were more likely to have a negative treatment response. The association in TLR5(rs5744174 remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4-16.3,p = 0.0002,q = 0.024. No other association withstood correction for multiple testing. Post hoc analyses showed that change in Patient Global score on a visual analogue scale (VAS and change in pain VAS were the main factors responsible for the association.We reproduced previously reported associations between genetic variation in the TLR10/1/6 gene cluster, TLR5

  8. Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice.

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    Manli Na

    Full Text Available RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic Staphylococcus aureus (S. aureus infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local S. aureus infection (e.g., skin infection might differ from their effects on a systemic infection.The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on S. aureus skin infections in mice.Abatacept (CTLA4 Ig, etanercept (anti-TNF treatment or PBS was given to NMRI mice subcutaneously inoculated with S. aureus strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups.Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups.Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for S. aureus skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

  9. Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

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    Way-Seah Lee

    2017-10-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

  10. ¿(Anti-TNF-¿ y tuberculosis pulmonar

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    Carlo Vinicio Caballero Uribe

    2006-01-01

    Full Text Available Presentación de una paciente con artritis reumatoide severa en tratamiento con inhibidores del Factor de Necrosis Tumoral (Anti-TNF, quien presenta además un cuadro de tuberculosis pulmonar. La artritis reumatoide es una enfermedad inflamatoria crónica de las articulaciones, que afecta en un inicio la membrana sinovial, pero que si no es tratada oportunamente lleva a daño estructural irreversible del sistema músculo-esquelético y eventualmente de otros sistemas orgánicos. Dentro de los criterios de la American College of Rheumatology se incluyen la Rigidez Matutina, Artritis de 3 o más articulaciones, Artritis simétrica, Nódulos reumáticos, Factor Reumatoideo y hallazgos radiográficos. Dentro de la patogenia de esta enfermedad, el Factor de Necrosis Tumoral es una citocina que juega un papel importante, una producción elevada de TNF-α se ha encontrado en la sinovial de estos pacientes, y por su capacidad de inducir la producción de otras citocinas, como IL-6, IL-17, GM-CSF, M-CSF, e incluso IL-1 y TNF-α (función autócrina, parecería que el TNF-α ejerce una acción “jerárquica” dentro de la llamada red de citocinas y una inhibición de su acción da como resultado un beneficio terapéutico en los pacientes con AR. Sin embargo, es conocido que la infección concurrente más frecuentemente informada con el uso de agentes biológicos (Anti-TNF es la TB, y la incidencia de ésta se ha incrementado desde el advenimiento de la terapia biológica. Por tanto, la descripción de este caso no corresponde a un hecho médico aislado, sino a una problemática actual y real. Este es el primer caso que se reporta en la Costa Caribe.

  11. Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn's Disease: A Comparison of Effectiveness and Safety.

    Science.gov (United States)

    Liu, Jinan; Sylwestrzak, Gosia; Ruggieri, Alexander P; DeVries, Andrea

    2015-07-01

    In recent years, there have been a number of pharmacological innovations for Crohn's disease (CD), a difficult-to-treat condition, including new treatment philosophies (e.g., top-down therapy) and new therapeutic options in terms of the agent and the route of administration. Three anti-tumor necrosis factor (anti-TNF-alpha) agents are available for use among CD patients in the United States: infliximab, an intravenous agent, and adalimumab and certolizumab pegol, 2 newer subcutaneous products. Infliximab is considered the "gold standard" because it has the longest clinical experience, and adalimumab and certolizumab pegol have each gained significant market share. To examine differences in effectiveness and safety between currently available intravenous and subcutaneous anti-TNF-alpha agents used to treat patients with CD. Data for this retrospective, administrative claims analysis were obtained from pharmacy and medical claims from major U.S. health plans geographically dispersed across 14 states during 2007-2011. Patients had at least 1 ICD-9-CM diagnosis for CD, 6 months pre-index eligibility, and initiated anti-TNF-alpha therapy on the index date. Patients in each cohort were propensity score matched on pre-index demographics, clinical characteristics, and baseline health care use. During the post-index period, age-sex adjusted incidence rate ratios (IRRs) of CD-related symptoms, infections, cancers, and hepatic-related conditions were compared using Cox (PH) models. The matched cohorts included 515 patients in each group, with an average age of 39 years. Median follow-up was 17.5 months in the intravenous cohort and 17.7 months in the subcutaneous cohort. In terms of effectiveness outcomes, age-sex adjusted IRRs for the subcutaneous group, with the intravenous cohort as a reference, were as follows: 0.61 (95% CI = 0.32-1.18, P = 0.14) for anal fissures; 0.97 (95% CI = 0.72-1.30, P = 0.85) for abscess; 1.08 (95% CI = 0.79-1.04, P = 0

  12. Efficacy and safety of combining intra-articular methylprednisolone and anti-TNF agent to achieve prolonged remission in patients with recurrent inflammatory monoarthritis.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    OBJECTIVE: To control local inflammation, the role of intra-articular corticosteroid is well established; similarly, with time there are more reports on the experience of intra-articular anti-TNF agent for localized joint inflammation. The aim of this study was to assess the safety, local tolerability and clinical response after combining intra-articular administration of corticosteroids and anti-TNF agents for recurrent inflammatory monoarthritis. METHODS: Patients with recurrent monoarthritis of the knee were recruited from our inflammatory arthritis clinics. These patients required intra-articular corticosteroids every 8-12 weeks, with good short-term results. Five such consecutive patients were invited to partake in this study. Patients were maintained on their baseline immunosuppressive therapy. After aspiration of knee joint, the involved joint was injected with 80mg of methylprednisolone mixed with 5ml of lignocaine 1%; this was followed by the injection of an anti-TNF agent. RESULTS: In majority of our patients (three out of five), combining anti-TNF agent and methylprednisolone led to prolonged anti-inflammatory response, and these patients remain in remission to date (mean follow-up of 12 months). These responders were noted to be naive to anti-TNF therapy. Conversely, the remaining two patients were found to be on baseline systemic anti-TNF therapy, and both of them failed to respond either partly or completely. CONCLUSION: Combining intra-articular corticosteroid and anti-TNF agent has proved to be safe in our cohort of patients. We conclude that in particular subset of patients who suffer from recurrent inflammatory monoarthritis or oligoarthritis, combination therapy of intra-articular corticosteroids and anti-TNF agents appears attractive and promising.

  13. Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Milena Iwaszko

    2018-01-01

    Full Text Available A natural killer group 2 member D (NKG2D acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF therapy is in rheumatoid arthritis (RA patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G, rs1049174 (C > G, and rs1154831 (C > A. Clinical response was evaluated according to the European League against Rheumatism (EULAR criteria at the 12th and 24th week. Both the NKG2D rs225336 and rs1049174 polymorphisms were significantly associated with efficacy of TNF inhibitors. Inefficient therapy was more frequently observed in patients with rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value = 0.003 and p-value = 0.004, respectively. The presence of the rs2255336 G or the rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p-value = 0.031, respectively. Moreover, patients carrying the rs2255336 or rs1049174 heterozygous genotype achieved better EULAR responses than patients with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively. Data from the present study provides evidence that NKG2D polymorphisms may affect response to anti-TNF inhibitors in RA patients.

  14. Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy

    NARCIS (Netherlands)

    van der Meer, Marrit; Hoving, Jan L.; Vermeulen, Marjolein I. M.; Herenius, Marieke M. J.; Tak, Paul P.; Sluiter, Judith K.; Frings-Dresen, Monique H. W.

    2011-01-01

    To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with

  15. Genetic Variation in the TLR5 Locus Is Associated with Anti-TNF Response Among Rheumatoid Arthritis Patients

    DEFF Research Database (Denmark)

    Sode, Jacob

    2014-01-01

    and interferon-gamma pathways were assessed in 538 anti-TNF naive Danish RA patients. Prospectively collected clinical data including functional status (HAQ), patient global score, smoking status, tender and swollen joint counts, treatments, rheumatoid factor (RF) status and C-reative protein (CRP) were obtained...... for seropositive RA in CARD8 (rs2043211), IL18 (rs187238) and TLR1 (rs4833095) (data not shown) but due to low power these results are preliminary. Conclusion: Our results confirm association between a TLR5 locus and EULAR response to anti-TNF treatment. Previous studies suggest that this polymorphism...

  16. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH

  17. Safety of herpes zoster vaccination among inflammatory bowel disease patients being treated with anti-TNF medications.

    Science.gov (United States)

    Khan, N; Shah, Y; Trivedi, C; Lewis, J D

    2017-10-01

    The risk of herpes zoster (HZ) is elevated in inflammatory bowel disease (IBD) patients treated with anti-TNF medications. While it is optimal to give herpes zoster vaccine prior to initiation of therapy clinical circumstances may not always allow this. To determine the safety of giving herpes zoster vaccine while patients are on anti-TNF therapy. We conducted a retrospective cohort study involving IBD patients who were followed in the Veterans Affairs (VA) healthcare system between 2001 and 2016. Patients who received herpes zoster vaccine while on anti-TNF medication were identified through vaccination codes and confirmed through individual chart review. Our outcome of interest was development of HZ between 0 and 42 days after herpes zoster vaccine administration. Fifty-six thousand four hundred and seventeen patients with IBD were followed in the VA healthcare system. A total of 59 individuals were on anti-TNF medication when they were given herpes zoster vaccine, and amongst them, 12 (20%) were also taking a thiopurine. Median age at the time of herpes zoster vaccine was 64.9 years and 95% of patients had a Charlson Comorbidity Index of ≥2. Median number of encounters within 42 days after receiving herpes zoster vaccine was two. No case of HZ was found within 0-42 days of HZV administration. Our data suggest that co-administering the herpes zoster vaccine to patients who are taking anti-TNF medications is relatively safe. This study significantly expands the evidence supporting the use of herpes zoster vaccine in this population, having included an elderly group of patients with a high Charlson Comorbidity Index who are likely at a much higher risk of developing HZ. © 2017 John Wiley & Sons Ltd.

  18. Lack of association of variants previously associated with anti-TNF medication response in rheumatoid arthritis patients: results from a homogeneous Greek population.

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    Maria I Zervou

    Full Text Available Treatment strategies blocking tumor necrosis factor (anti-TNF have proven very successful in patients with rheumatoid arthritis (RA, showing beneficial effects in approximately 50-60% of the patients. However, a significant subset of patients does not respond to anti-TNF agents, for reasons that are still unknown. The aim of this study was to validate five single nucleotide polymorphisms (SNPs of PTPRC, CD226, AFF3, MyD88 and CHUK gene loci that have previously been reported to predict anti-TNF outcome. In addition, two markers of RA susceptibility, namely TRAF1/C5 and STAT4 were assessed, in a cohort of anti-TNF-treated RA patients, from the homogeneous Greek island of Crete, Greece. The RA patient cohort consisted of 183 patients treated with either of 3 anti-TNF biologic agents (infliximab, adalimumab and etanercept from the Clinic of Rheumatology of the University Hospital of Crete. The SNPs were genotyped by TaqMan assays or following the Restriction Fragments Length Polymorphisms (RFLPs approach. Disease activity score in 28 joints (DAS28 at baseline and after 6 months were available for all patients and analysis of good versus poor response at 6 months was performed for each SNP. None of the 7 genetic markers correlated with treatment response. We conclude that the gene polymorphisms under investigation are not strongly predictive of anti-TNF response in RA patients from Greece.

  19. Lack of association of variants previously associated with anti-TNF medication response in rheumatoid arthritis patients: results from a homogeneous Greek population.

    Science.gov (United States)

    Zervou, Maria I; Myrthianou, Efsevia; Flouri, Irene; Plant, Darren; Chlouverakis, Gregory; Castro-Giner, Francesc; Rapsomaniki, Panayiota; Barton, Anne; Boumpas, Dimitrios T; Sidiropoulos, Prodromos; Goulielmos, George N

    2013-01-01

    Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. However, a significant subset of patients does not respond to anti-TNF agents, for reasons that are still unknown. The aim of this study was to validate five single nucleotide polymorphisms (SNPs) of PTPRC, CD226, AFF3, MyD88 and CHUK gene loci that have previously been reported to predict anti-TNF outcome. In addition, two markers of RA susceptibility, namely TRAF1/C5 and STAT4 were assessed, in a cohort of anti-TNF-treated RA patients, from the homogeneous Greek island of Crete, Greece. The RA patient cohort consisted of 183 patients treated with either of 3 anti-TNF biologic agents (infliximab, adalimumab and etanercept) from the Clinic of Rheumatology of the University Hospital of Crete. The SNPs were genotyped by TaqMan assays or following the Restriction Fragments Length Polymorphisms (RFLPs) approach. Disease activity score in 28 joints (DAS28) at baseline and after 6 months were available for all patients and analysis of good versus poor response at 6 months was performed for each SNP. None of the 7 genetic markers correlated with treatment response. We conclude that the gene polymorphisms under investigation are not strongly predictive of anti-TNF response in RA patients from Greece.

  20. Mucosal healing with thalidomide in refractory Crohn's disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review.

    Science.gov (United States)

    Scribano, Maria Lia; Cantoro, Laura; Marrollo, Marzia; Cosintino, Rocco; Kohn, Anna

    2014-07-01

    Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNFtherapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

  1. IgA deficiency evidence after anti-TNF-α treatment in a psoriatic arthritis patient: case report

    Directory of Open Access Journals (Sweden)

    R. Scarpa

    2012-03-01

    Full Text Available It is known that the use of anti-TNF-α drugs is related to an increased incidence of infective diseases. This therapy can not be administered to patients having active infections and it has to be considered with caution in case of acquired or congenital immunodeficiency diseases. We report the case of a 28-years-old man affected by psoriatic arthritis; he developed some infections during treatment with TNF-α blockers. The infections were caused by a selective IgA deficiency, that was not evident before the anti-TNF-α blockers administration and disappeared after withdrawing the biological therapy. This case-report draws our attention to the possibility of cases of subclinical immunodeficiency, unknown by the patients, but important in the prognosis and in the therapeutic approach to these diseases. Therefore, it is important to evaluate carefully the immunologic status of patients during the pre-therapeutic screening for TNF-α blocking therapy.

  2. Higher 25-hydroxyvitamin D levels are associated with greater odds of remission with anti-tumour necrosis factor-α medications among patients with inflammatory bowel diseases.

    Science.gov (United States)

    Winter, R W; Collins, E; Cao, B; Carrellas, M; Crowell, A M; Korzenik, J R

    2017-03-01

    Vitamin D has been linked to disease activity among patients with inflammatory bowel diseases (IBD). Prior investigation has also suggested that vitamin D levels may affect duration of therapy with anti-tumour necrosis factor-α (anti-TNF-α) medications among patients with IBD. To evaluate the relationship between vitamin D levels and odds of reaching remission while on an anti-TNF-α medication. A total of 521 IBD patients enrolled in the Brigham and Women's IBD Centre database were eligible for inclusion. Patients treated with anti-TNFtherapy who had vitamin D levels drawn within 6 months prior or 2 weeks after initiation of anti-TNF-α medication and who had reported remission status at 3 months were included. A logistic regression model adjusting for age, gender, IBD diagnosis, anti-TNF-α medication (infliximab vs. adalimumab) and first or subsequent anti-TNF-α medication was used to identify the effect of vitamin D level on initial response to anti-TNFtherapy. A total of 173 patients were included in the final analysis. On logistic regression, patients with normal vitamin D levels n = 122 at the time of anti-TNF-α medication initiation had a 2.64 increased odds of remission at 3 months compared to patients with low vitamin D levels n = 51 when controlling for age, gender, diagnosis, type of anti-TNF-α medication and first or subsequent anti-TNF-α medication (OR = 2.64, 95% CI = 1.31-5.32, P = 0.0067). These findings suggest that vitamin D levels may influence initial response to anti-TNF-α medication and that low vitamin D levels may pre-dispose patients to decreased odds of remission. © 2017 John Wiley & Sons Ltd.

  3. Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

    International Nuclear Information System (INIS)

    Wilson, Christy M.; Gaber, M. Waleed; Sabek, Omaima M.; Zawaski, Janice A.; Merchant, Thomas E.

    2009-01-01

    Purpose: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. Methods and Materials: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidate the role of TNF in leukocyte adhesion and vessel diameter. Results: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. Conclusions: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain's microvascular network from the acute damage following RT.

  4. Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

    Science.gov (United States)

    de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

    2014-01-01

    To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  5. Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy

    DEFF Research Database (Denmark)

    Bank, S.; Andersen, P. S.; Burisch, J.

    2018-01-01

    Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined hi...

  6. Hanseníase virchowiana associada ao uso de inibidor do fator de necrose tumoral α: relato de caso Lepromatous leprosy associated with the use of anti-TNF α therapy: case report

    Directory of Open Access Journals (Sweden)

    Daniele S Freitas

    2010-06-01

    Full Text Available A terapia anti-TNFα tem sido amplamente utilizada em diversas artropatias inflamatórias crônicas, em especial artrite reumatoide (AR. No entanto, há preocupações quanto à segurança e ao risco de doenças infecciosas nos pacientes. O objetivo deste artigo é descrever um caso de hanseníase, forma virchowiana, em paciente com AR em uso de terapia anti-TNFα. Dessa forma, a vigilância dos eventos adversos deve ser rigorosa, especialmente no que diz respeito às doenças infecciosas. É recomendada investigação apropriada de lesões cutâneas em paciente recebendo terapia anti-TNFα, visto que o quadro clínico inicial pode ser inespecífico, especialmente em regiões endêmicas como o Brasil.TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFa therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.

  7. Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome

    DEFF Research Database (Denmark)

    Sode, Jacob; Vogel, Ulla; Bank, Steffen

    2014-01-01

    (relDAS28) were used as secondary outcomes. Subgroup analyses were stratified according to smoking status, type of anti-TNF drug and IgM-Rheumatoid Factor (IgM-RF) status. False discovery rate (FDR) controlling was used to adjust for multiple testing. RESULTS: Statistically significant associations...... in independent validation cohorts and augmented by assessing cytokine levels and activities of the relevant gene products....

  8. The PRECiSE 2 trial of certolizumab pegol, a new PEGylated anti-TNF agent, in the treatment of Crohn's disease - An interview with David A Schwartz, 13 June 2007

    Directory of Open Access Journals (Sweden)

    David A Schwartz

    2008-03-01

    Full Text Available David A SchwartzVanderbilt University Medical Center, Nashville, TN, USAContext: Certolizumab pegol (CDP 870 is a new anti-tumor necrosis factor (TNF therapy currently in development for the treatment of Crohn’s disease, rheumatoid arthritis, and psoriasis. Certolizumab pegol is the first PEGylated biologic anti-TNF agent and has a high binding affinity for TNF. Dr. Schwartz was an investigator of the PRECiSE (PEGylated Antibody Fragment Evaluation in Crohn’s Disease Safety and Efficacy 2 trial of certolizumab pegol in patients with Crohn’s disease.Keywords: certolizumab pegol, PRECiSE 2 trial, Crohn’s disease

  9. Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome

    DEFF Research Database (Denmark)

    Sode, Jacob; Vogel, Ulla; Bank, Steffen

    2014-01-01

    OBJECTIVE: Many patients with rheumatoid arthritis (RA) benefit from tumor necrosis factor-α blocking treatment (anti-TNF), but about one third do not respond. The objective of this study was to replicate and extend previously found associations between anti-TNF treatment response and genetic...... logistic regression analyses were performed to test associations between genotypes and treatment response at 3-6 months using the European League Against Rheumatism (EULAR) response criterion. American College of Rheumatology treatment response (ACR50) and relative change in 28-joint disease activity score.......36-0.98), p = 0.040, q = 0.76). Current smokers who carried the NLRP3(rs4612666) variant allele were less likely to benefit from anti-TNF treatment (OR = 0.24 (0.10-0.56), p = 0.001, q = 0.04). CONCLUSIONS: In a population of Danish RA patients, we confirm the NLRP3 gene as associated with EULAR anti...

  10. Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management

    Directory of Open Access Journals (Sweden)

    Dong Il Park

    2018-01-01

    Full Text Available Because anti-tumor necrosis factor (anti-TNF therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

  11. Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

    2015-08-20

    Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

  12. Measuring patients’ satisfaction with their anti-TNF treatment in severe Crohn’s disease: scoring and psychometric validation of the Satisfaction for PAtients in Crohn’s diseasE Questionnaire (SPACE-Q©

    Directory of Open Access Journals (Sweden)

    Gilet H

    2014-12-01

    Full Text Available Hélène Gilet,1 Benoit Arnould,1 Fatoumata Fofana,1 Pierre Clerson,2 Jean-Frédéric Colombel,10 Olivier D’Hondt,2 Patrick Faure,4 Hervé Hagège,5 Maria Nachury,3 Stéphane Nahon,6 Gilbert Tucat,7 Luc Vandromme,8 Ines Cazala-Telinge,9 Emmanuel Thibout9 1HEOR and Strategic Market Access, Mapi, Lyon, France; 2Orgamétrie, Roubaix, France; 3Hôpital Claude Huriez, Lille, France; 4Clinique Saint-Jean du Languedoc, Toulouse, France; 5Centre Hospitalier Intercommunal, Créteil, France; 6Centre Hospitalier Intercommunal, Le Raincy Montfermeil, France; 7Gastroenterologist, Private Clinical Practice, Paris, France; 8Gastroenterologist, Private Clinical Practice, Reims, France; 9Abbvie France, Rungis, France; 10Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Severe Crohn’s disease management includes anti-tumor necrosis factor (anti-TNF drugs that differ from early-stage treatments regarding efficacy, safety, and convenience. This study aimed to finalize and psychometrically validate the Satisfaction for PAtients in Crohn’s diseasE Questionnaire (SPACE-Q©, developed to measure satisfaction with anti-TNF treatment in patients with severe Crohn’s disease. Methods: A total of 279 patients with severe Crohn’s disease receiving anti-TNF therapy completed the SPACE-Q 62-item pilot version at inclusion and 12 and 13 weeks after first anti-TNF injection. The final SPACE-Q scoring was defined using multitrait and regression analyses and clinical relevance considerations. Psychometric validation included clinical validity against Harvey–Bradshaw score, concurrent validity against Treatment Satisfaction Questionnaire for Medication (TSQM, internal consistency reliability, test–retest reliability, and responsiveness against the patient global impression of change (PGIC.Results: Quality of completion was good (55%–67% of patients completed all items. Four items were removed from the questionnaire. Eleven scores were defined

  13. Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy.

    Science.gov (United States)

    Van der Meer, Marrit; Hoving, Jan L; Vermeulen, Marjolein I M; Herenius, Marieke M J; Tak, Paul P; Sluiter, Judith K; Frings-Dresen, Monique H W

    2011-01-01

    To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with respect to work participation. Experiences regarding work participation varied and ranged from fatigue at work, having no job control, not being understood by the work environment or difficulty dealing with emotions as a result of interaction within the work environment. Support by health care professionals for work participation was considered important, especially concerning social or psychological issues. Advice in becoming aware of one's changes in abilities was highly appreciated, as was the availability of professional advice in times of an urgent work issue due to RA. Employees mentioned an increase in social support at work and job control as important facilitating factors for work participation. Although patients with RA report improvement in their work functioning after starting anti-TNF therapy, employees continue facing challenges in working life due to RA. For support concerning work participation, it is recommended that health care professionals are more aware of work-related problems in patients with RA treated with anti-TNF therapy.

  14. The ratio Neutrophil/Lymphocyte and Platelet/Lymphocyte in patient with Rheumatoid Arthritis that are Treating with Anti-TNF

    Directory of Open Access Journals (Sweden)

    İsmail Boyraz

    2014-06-01

    Full Text Available OBJECTIVES: Rheumatoid arthritis (RA is a chronic inflammatory disorder with unknown etiology. RA is characterized by a variable course of remissions and relapses, and subclinical inflammation persists between the disease exacerbations. Anti-TNF therapies have become more often preferred in recent years in the treatment of RA. The aim of the present study was to determine the relationship between N/L and P/L ratios and subclinical inflammation in patients with RA who achieved remission with anti-TNF therapy. METHODS: The present study was a retrospective, controlled and multicenter study. The present study reviewed the medical records of the patients who were on follow-up in the outpatient clinics of the Department of Physical Therapy in Abant İzzet Baysal University and Harran University due to rheumatoid arthritis (RA and who achieved remission with anti-TNF therapy.A total of 80 patients in the inactive phase of RA and 45 healthy subjects in the control group were included in the study. Hemogram results of the people were examined retrospectively. RESULTS: There was significant difference between the patient and the control group in terms of platelet ratio and lymphocyte and neutrophil ratio. There was no significant difference between the group in terms of N/L and P/L ratios.CONCLUSIONS:  In the current study, we found significant differences between the patient and the control group in terms of neutrophil, lymphocyte, and platelet counts; however, there was no significant difference between the two groups in terms of N/L and P/L ratios. These findings suggest that therapies with anti-TNF agents in patients with RA achieved complete control of inflammation. 

  15. Effects of Anti-TNF Alpha Drugs on Disability in Patients with Rheumatoid Arthritis: Long-Term Real-Life Data from the Lorhen Registry

    Directory of Open Access Journals (Sweden)

    Matteo Filippini

    2014-01-01

    Full Text Available This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years.

  16. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

    Science.gov (United States)

    Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

    2015-07-01

    Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.

  17. Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

    Directory of Open Access Journals (Sweden)

    Ana Esteve-Solé

    2017-09-01

    Full Text Available BackgroundAlthough anti-TNF-α monoclonal antibodies are considered safe during pregnancy, there are no studies on the development of the exposed-infant immune system. The objective was to study for the first time the impact of throughout pregnancy exposure to anti-TNF-α has an impact in the development of the infant’s immune system, especially B cells and the IL-12/IFN-γ pathway.MethodsProspective study of infants born to mothers with inflammatory bowel disease treated throughout pregnancy with anti-TNF-α (adalimumab/infliximab. Infants were monitored both clinically and immunologically at birth and at 3, 6, 12, and 18 months.ResultsWe included seven patients and eight healthy controls. Exposed infants had detectable levels of anti-TNF-α until 6 months of age; they presented a more immature B- and helper T-phenotype that normalized within 12 months, with normal immunoglobulin production and vaccine responses. A decreased Treg cell frequency at birth that inversely correlated with mother’s peripartum anti-TNF-α levels was observed. Also, a decreased response after mycobacterial challenge was noted. Clinically, no serious infections occurred during follow-up. Four of seven had atopia.ConclusionThis study reveals changes in the immune system of infants exposed during pregnancy to anti-TNF-α. We hypothesize that a Treg decrease might facilitate hypersensitivity and that defects in IL-12/IFN-γ pathway might place the infant at risk of intracellular infections. Pediatricians should be aware of these changes. Although new studies are needed to confirm these results, our findings are especially relevant in view of a likely increase in the use of these drugs during pregnancy in the coming years.

  18. Is there a benefit from the concomitant use of immunosupression with anti-TNF in Crohn's disease; heads or tails?

    Science.gov (United States)

    Lakatos, Peter Laszlo

    2009-09-01

    Over the last some years the increasing knowledge on the pathogenesis of Crohn's disease led to the development of a number of biological agents targeting specific molecules involved in gut inflammation, first of all TNF-alpha and its receptors. Infliximab, adalimumab and certolizumab have been successful in inducing and maintaining remission in Crohn's disease at both short and long term. This was recently confirmed by a Cochrane meta-analysis and also open label extension follow-up and cohort studies. Emerging new data however indicate that combination therapy with infliximab-azathioprine appears to have added benefit in inducing steroid-free remission and mucosal healing than either infliximab or azathioprine alone in azathioprine-naïve patients with early disease. Similarly the combination of steroids induction and infliximab was efficacious in luminal Crohn's disease. In contrast, there seems to be no synergism between methotrexate and infliximab. It is also less clear whether it is beneficial to use short or long-term infliximab-azathioprine combination in patients who previously failed therapy with azathioprine. In contrast, combination may potentially be associated with increased risk for infection and cancer. In case control-studies, especially the combination of steroids and anti-TNF and older age increased the risk for infectious complications, while scattered case reports point to the potentially increased risk of a rare form of non-Hodgkin's lymphoma (Hepatosplenic T cell lymphoma) with the use of azathioprine-anti-TNF combination. The aim of this review is to summarize the benefits and risks for the use combination therapy with TNF-alpha inhibitors in the treatment of Crohn's disease.

  19. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Nordgaard-Lassen, Inge; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X...

  20. Perfil lipídico e uso de anti-TNF

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Ferraz Filho

    2013-10-01

    Full Text Available O uso do anti-TNF alfa tem sido associado a várias alterações no perfil lipídico, embora o estudo dessas alterações tenha gerado resultados que ainda são conflitantes. O conhecimento desse fato é de grande importância quando se observa a associação entre doenças reumáticas e aterogenêse acelerada. Esta pesquisa foi feita com o intuito de verificar alterações no perfil lipídico de usuários de anti-TNF-α na população do sul do Brasil e sua associação com tempo de uso, indicações, gênero do paciente e tipo de anti-TNF. Para tanto, analisaram-se os perfis de colesterol total (TC, HDL colesterol (HDLc, LDL colesterol (LDLc, índice aterogênico (IAT e triglicerídeos (TGs de 58 pacientes (42 com artrite reumatoide e 16 com espondiloartrites antes e depois do uso desse medicamento por um tempo mediano de 16,0 meses. Não se observaram alterações nos níveis de CT, HDLc, LDLc e IAT (P = NS. Todavia, houve um aumento significativo nos níveis de TGs (P = 0,03. A diferença mediana dos valores de TGs entre primeira e segunda medidas foi de 16 mg/dL, e esse aumento não estava associado ao gênero do paciente, tempo de uso, indicação de uso ou tipo de anti-TNF-α (P = NS. Concluiu-se que o uso de anti TNF-α está associado com aumento nos valores de TGs.

  1. Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment

    Directory of Open Access Journals (Sweden)

    Dong Il Park

    2018-01-01

    Full Text Available Because anti-tumor necrosis factor (anti-TNF therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

  2. Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    2015-01-01

    Full Text Available Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week. During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started.

  3. An update on anti-TNF agents in ulcerative colitis

    NARCIS (Netherlands)

    Samaan, Mark A.; Bagi, Preet; Vande Casteele, Niels; D'Haens, Geert R.; Levesque, Barrett G.

    2014-01-01

    Anti-tumor necrosis factor-α agents are key therapeutic options for the treatment of ulcerative colitis. Their efficacy and safety have been shown in large randomized controlled trials. The key evidence gained from these trials of infliximab, adalimumab, and golimumab is reviewed along with their

  4. Safety and efficacy of anti-tumor necrosis factor α therapy in ten patients with recent-onset refractory reactive arthritis.

    Science.gov (United States)

    Meyer, Alain; Chatelus, Emmanuel; Wendling, Daniel; Berthelot, Jean-Marie; Dernis, Emmanuelle; Houvenagel, Eric; Morel, Jacques; Richer, Olivier; Schaeverbeke, Thierry; Gottenberg, Jacques-Eric; Sibilia, Jean

    2011-05-01

    There are few treatments for reactive arthritis (ReA). Since concentrations of tumor necrosis factor α (TNFα) are high in the serum and joints of patients with persistent ReA, this cytokine could be targeted in patients who do not respond to nonsteroidal antiinflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). We under-took this study to investigate the safety and efficacy of TNF antagonists in patients with recent-onset and refractory ReA. All French rheumatology and internal medicine practitioners registered on the Club Rhumatisme et Inflammation web site were asked to report on patients with ReA (defined by the criteria of the Third International Workshop on Reactive Arthritis) who had received anti-TNF therapy within the 12 months following the triggering infection. Tolerance and efficacy were retrospectively assessed using a standardized questionnaire. Ten patients with ReA previously refractory to NSAIDs and DMARDs, for which there was clinical and microbiologic evidence of a triggering bacterial infection, received anti-TNF therapy within a median of 6 months (range 2-12 months) between the beginning of ReA and the initiation of the treatment. The median followup was 20.6 months (range 6-50 months). We observed no severe adverse event and no infection related to the bacterium that triggered the ReA. Anti-TNF therapy was rapidly effective in 9 patients (90%), as shown by the rapid effect on a visual analog scale pain score, tender joint count, swollen joint count, and extraarticular manifestations, and by the corticosteroid-sparing effect. Anti-TNF therapy appears to be a safe and effective treatment of rheumatic and extraarticular manifestations in patients with recent-onset and refractory ReA, with a corticosteroid-sparing effect. Thus, TNFα could be a relevant target for ReA therapy.

  5. Rocky Mountain Spotted Fever in a patient treated with anti-TNF-alpha inhibitors.

    Science.gov (United States)

    Mays, Rana M; Gordon, Rachel A; Durham, K Celeste; LaPolla, Whitney J; Tyring, Stephen K

    2013-03-15

    Rocky Mountain Spotted Fever (RMSF) is a tick-bourne illness, which can be fatal if unrecognized. We discuss the case of a patient treated with an anti-TNF-alpha inhibitor for rheumatoid arthritis who later developed a generalized erythematous macular eruption accompanied by fever. The clinical findings were suggestive of RMSF, which was later confirmed with serology. Prompt treatment with doxyclycine is recommended for all patients with clinical suspicion of RMSF.

  6. New Onset Autoimmune Hepatitis during Anti-Tumor Necrosis Factor-Alpha Treatment in Children.

    Science.gov (United States)

    Ricciuto, Amanda; Kamath, Binita M; Walters, Thomas D; Frost, Karen; Carman, Nicholas; Church, Peter C; Ling, Simon C; Griffiths, Anne M

    2018-03-01

    To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use. We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center. Patients with alanine aminotransferase (ALT) ≥×2 the upper limit of normal were included. The incidence, evolution, and risk factors for liver injury were examined with univariate and multivariable proportional hazards regression. Causality was assessed using the Roussel-Uclaf Causality Assessment Method. The index case, a teenage girl with Crohn's disease, developed elevated liver enzymes and features of autoimmune hepatitis on liver biopsy 23 weeks after starting infliximab. The injury resolved entirely within 4 months of withdrawing infliximab without additional therapy. Overall, 7.7% of our cohort developed new ALT elevations while on anti-TNF. Most ALT elevations were mild and transient and attributable to alternate etiologies. No additional clear cases of autoimmune hepatitis were identified. Transient liver enzyme abnormalities are relatively common among anti-TNF-treated children. Anti-TNF-related DILI with autoimmune features is rare but must be recognized so that therapy can be stopped. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A sonographic lesion index for Crohn's disease helps monitor changes in transmural bowel damage during therapy.

    Science.gov (United States)

    Zorzi, Francesca; Stasi, Elisa; Bevivino, Gerolamo; Scarozza, Patrizio; Biancone, Livia; Zuzzi, Sara; Rossi, Carla; Pallone, Francesco; Calabrese, Emma

    2014-12-01

    Therapeutic antibodies against tumor necrosis factor α (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but little is known about the effects of anti-TNF agents on structural damage in the intestine. Small-intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD [SLIC]) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index scores less than 150. We observed significant improvements in SLIC scores and subscores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and subscores and index classes were improved significantly in patients with vs without clinical responses. Controls had no improvements in terms of CD activity index or SLIC scores, or index classes. Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. A BioDesign Approach to Obtain High Yields of Biosimilars by Anti-apoptotic Cell Engineering: a Case Study to Increase the Production Yield of Anti-TNF Alpha Producing Recombinant CHO Cells.

    Science.gov (United States)

    Gulce Iz, Sultan; Inevi, Muge Anil; Metiner, Pelin Saglam; Tamis, Duygu Ayyildiz; Kisbet, Nazli

    2018-01-01

    Recent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used. Adalimumab is a fully human anti-TNF mAb among the top-selling mAb products in recent years as a biosimilar. Products from mammalian cell bioprocesses are a derivative of cell viability and metabolism, which is mainly disrupted by cell death in bioreactors. Thus, different strategies are used to increase the product yield. Suppression of apoptosis, also called anti-apoptotic cell engineering, is the most remarkable strategy to enhance lifetime of cells for a longer production period. In fact, using anti-apoptotic cell engineering as a BioDesign approach was inspired by nature; nature gives prolonged life span to some cells like stem cells, tumor cells, and memory B and T cells, and researchers have been using this strategy for different purposes. In this study, as a biomimicry approach, anti-apoptotic cell engineering was used to increase the anti-TNF-α mAb production from the humanized anti-TNF-α mAb producing stable CHO cell line by Bcl-xL anti-apoptotic protein. It was shown that transient transfection of CHO cells by the Bcl-xL anti-apoptotic protein expressing plasmid prolonged the cell survival rate and protected cells from apoptosis. The transient expression of Bcl-xL using CHO cells enhanced the anti-TNF-α production. The production of anti-TNF-α in CHO cells was increased up to 215 mg/L with an increase of 160% after cells were transfected with Bcl-xL expressing plasmid

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

    Science.gov (United States)

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

    2016-08-23

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

  10. How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

    Science.gov (United States)

    Ward, Mark G; Irving, Peter M; Sparrow, Miles P

    2015-10-28

    In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

  11. Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Sørensen, Signe Bek; Nielsen, J V; Bo Bojesen, Anders

    2016-01-01

    BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. AIM......2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers...... in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms...

  12. Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.

    Science.gov (United States)

    Lew, Daniel; Yoon, Soon Man; Yan, Xiaofei; Robbins, Lori; Haritunians, Talin; Liu, Zhenqiu; Li, Dalin; McGovern, Dermot Pb

    2017-10-28

    To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA ( P = 0.04) and IgG-ASCA ( P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions ( P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. Our study shows 1 in 5 IBD patients experience an adverse

  13. Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Ruxandra Calin

    2017-07-01

    Full Text Available A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF therapy is reported here. The patient required prolonged treatment with doxycycline–ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment.

  14. Efeito do anti-TNF-α em implantes endometriais no peritônio de ratas

    Directory of Open Access Journals (Sweden)

    William Kondo

    Full Text Available OBJETIVO: Avaliar o efeito da terapia anti-TNF-α no tratamento de implantes endometriais no peritônio de ratas. MÉTODOS: Os implantes endometrióticos foram induzidos cirurgicamente em 120 ratas Wistar-Albino. Os animais foram aleatoriamente distribuídos em 4 grupos. O grupo C (n=36 recebeu uma injeção intraperitoneal de 0,2ml de solução salina. O grupo L (n=41 recebeu uma injeção subcutânea de 1mg/kg de leuprolide. O grupo I5 (n=20 recebeu uma injeção subcutânea de 5mg/kg de anticorpo monoclonal anti-fator de necrose tumoral (TNF a (infliximab. O grupo I10 (n=20 recebeu uma injeção subcutânea de 10mg/kg de infliximab. As ratas foram sacrificadas após 21 dias para se avaliar o tamanho dos implantes e a expressão do TNF-α. RESULTADOS: O tratamento com leuprolide promoveu uma redução absoluta na área de superfície do implante comparado com o grupo C (+14mm vs. 0mm; p=0,013 e com o grupo I10 (+14mm vs. +5mm; p=0,018. Da mesma forma, uma redução percentual da area de superfície do implante foi observada comparando o grupo L com o grupo C (+33,3% vs. 0%; p=0,005 e com o grupo I10 (+33,3% vs. +18,3%; p=0,027. O tratamento com infliximab não foi capaz de diminuir a área de superfície do implante comparado com o grupo C. A expressão de TNF-α reduziu nos grupos L, I5 e I10 comparado com o grupo C (505,6µm² vs. 660,5µm² vs. 317,2µm² vs. 2519,3µm², respectivamente; p<0,001. CONCLUSÃO: A terapia anti-TNF-α reduziu a expressão de TNF-α nos implantes endometrióticos mas não reduziu a área de superfície da lesão.

  15. Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administered between 2008 and 2012 in a cohort of rheumatoid arthritis patients.

    Science.gov (United States)

    Alvarez Rivas, Noelia; Vazquez Rodriguez, Tomas R; Miranda Filloy, Jose A; Garcia-Porrua, Carlos; Sanchez-Andrade Fernández, Amalia

    2017-05-25

    To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. Increased Prevalence of Human Polyomavirus JC Viruria in Chronic Inflammatory Rheumatic Diseases Patients in Treatment with Anti-TNF α: A 18 Month Follow-Up Study.

    Science.gov (United States)

    Rodio, Donatella Maria; Anzivino, Elena; Mischitelli, Monica; Bellizzi, Anna; Scrivo, Rossana; Scribano, Daniela; Conte, Gianlorenzo; Prezioso, Carla; Trancassini, Maria; Valesini, Guido; Palamara, Anna Teresa; Pietropaolo, Valeria

    2016-01-01

    Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients.

  17. Effects of Combination Therapy With Immunomodulators on Trough Levels and Antibodies Against Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease: A Meta-analysis.

    Science.gov (United States)

    Qiu, Yun; Mao, Ren; Chen, Bai-Li; Zhang, Sheng-Hong; Guo, Jing; He, Yao; Zeng, Zhi-Rong; Ben-Horin, Shomron; Chen, Min-Hu

    2017-09-01

    It is not clear whether combination therapy with immunomodulators affects the immunogenicity of tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel disease. We performed a meta-analysis to quantify the effects of combined immunomodulator therapy on the presence of antibodies against TNF antagonists (antidrug antibodies [ADAs]) and trough levels of anti-TNF agents. We systematically searched publication databases for studies that reported prevalence of ADAs in patients who received anti-TNF agents. Raw data from studies that met the inclusion criteria were pooled to determine effect estimates. We performed subgroup and metaregression analyses to determine the level of heterogeneity among study outcomes. We analyzed findings from 35 studies that met inclusion criteria (results reported from 6790 patients with inflammatory bowel disease). The pooled risk ratio for formation of ADAs in patients receiving combined therapy with immunomodulators, versus that of patients receiving anti-TNF monotherapy, was 0.49 (95% confidence interval, 0.41-0.59; P immunomodulators (standardized mean difference, 0.11; 95% confidence interval, 0.19-0.41; P = .47). Subgroup analyses of patients treated with different TNF antagonists revealed no difference in the formation of ADAs (P = .50 for interaction); the protective effect of immunomodulators did not differ with type of drug patients were given (methotrexate vs thiopurines), or assay for ADA. We observed heterogeneity only among studies of patients with ulcerative colitis (I 2  = 76%). Funnel plot and Egger test analyses indicated publication bias in the studies (P = .001). In a meta-analysis of published studies, we associated combined treatment with immunomodulators with reduced risk of formation of antibodies against TNF antagonists in patients with inflammatory bowel disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factortherapy in inflammatory arthropathies. Associations with aortic stiffness.

    Science.gov (United States)

    Angel, Kristin; Provan, Sella Aarrestad; Mowinckel, Petter; Seljeflot, Ingebjørg; Kvien, Tore Kristian; Atar, Dan

    2012-11-01

    Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Forty-eight patients who started with anti-TNFtherapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Anti-TNFtherapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNFtherapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. Anti-TNFtherapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

    OpenAIRE

    Seto, Wai-Kay

    2015-01-01

    Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negati...

  20. Targeted anti-TNF therapy in severe sarcoidosis: towards precision medicine

    NARCIS (Netherlands)

    Crommelin, H.A.

    2018-01-01

    Sarcoidosis is a multisystem, granulomatous disorder of unknown etiology. The disease has many clinical phenotypes, ranging from asymptomatic and self-limiting to severe and life threatening disease. Virtually any organ can be involved, but pulmonary involvement is seen in approximately 90% of

  1. Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

    OpenAIRE

    Francesco Caso; Luisa Costa; Donato Rigante; Orso Maria Lucherini; Paolo Caso; Vittoria Bascherini; Bruno Frediani; Rolando Cimaz; Edoardo Marrani; Laura Nieves-Martín; Mariangela Atteno; Carmela G. L. Raffaele; Giusyda Tarantino; Mauro Galeazzi; Leonardo Punzi

    2014-01-01

    Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molec...

  2. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

    Science.gov (United States)

    Kirchgesner, J; Lemaitre, M; Rudnichi, A; Racine, A; Zureik, M; Carbonnel, F; Dray-Spira, R

    2017-01-01

    Management of inflammatory bowel disease (IBD) has evolved in the last decade. To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected. © 2016 John Wiley & Sons Ltd.

  3. Indirect comparison for Anti-TNF drugs in moderate to severe ulcerative colitis

    Directory of Open Access Journals (Sweden)

    M. Galván-Banqueri

    2015-01-01

    Full Text Available Objective: To compare the relative efficacy of infliximab, adalimumab and golimumab through adjusted indirect treatment comparisons (ITCs. Methods: An exhaustive search was performed until October 2013. Databases consulted were MEDLINE, EMBASE, the Cochrane Library, the Centre for Reviews and Dissemination and the Web of Science. Randomized control trials (RCTs comparing the efficacy of infliximab, adalimumab or golimumab versus placebo, in terms of clinical remission, clinical response and mucosal healing, were included. In the case that more than one RCT fulfilled the inclusion criteria for the same drug, a metanalysis was undertaken using a fixed effects model. ITCs were carried out using the method proposed by Bucher et al. Results: 6 RCTs published in 5 papers were included: 2 for infliximab (ACT 1 and ACT 2, 2 for adalimumab (ULTRA 1 y ULTRA 2 and 2 for golimumab (PURSUIT-SC y PURSUIT-M.In these RTCs, each biological agent was superior in efficacy to placebo. The results of the adjusted ITC are the following. In relation to the clinical remission, in the induction and maintenance period, there are no statistically significant differences between the three anti-TNF drugs. In relation to the clinical response and mucosal healing, in the induction period, there are statistically significant differences between infliximab and adalimumab. Conclusion: In view of the results obtained, infliximab, adalimumab and golimumab appear to be similarly effective therapeutic alternatives. Therefore, other considerations such as safety, tolerance and cost-effectiveness should be taken into account in order to select the most appropriate treatment

  4. Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti–Tumor Necrosis Factor α Therapy

    Science.gov (United States)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2013-01-01

    Objective Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (ΔDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ΔDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections

  5. Combined anti-tumor necrosis factortherapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

    Directory of Open Access Journals (Sweden)

    Carl K Edwards

    2012-12-01

    Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNFtherapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNFtherapy. Furthermore, combination DMARD and anti-TNFtherapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

  6. Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.

    Science.gov (United States)

    Chiang, Chi-Huei

    2006-10-31

    Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation.

  7. Perfuração do colo por colite amebiana invasiva durante terapia anti-TNF para espondiloartrite♧

    Directory of Open Access Journals (Sweden)

    Juan Pablo Restrepo

    2014-12-01

    Full Text Available O bloqueio do TNF tem tido sucesso no tratamento de algumas doenças reumáticas, como a espondiloartrite. Relatam-se muitas complicações infecciosas com a terapia anti-TNF, principalmente infecções bacterianas, micobacterianas, virais e fúngicas. A Entamoeba histolytica é um protozoário extracelular que causa principalmente colite e abscesso hepático, sendo que a perfuração intestinal é uma complicação rara, com alta mortalidade. O TNF é considerado o principal mediador da imunidade celular contra a amebíase. Inicialmente, é quimiotático para a E. histolytica, potencializando sua adesão ao enterócito por meio da lectina galactose-inibível, e depois ativando os macrófagos para matarem a ameba pela liberação de NO; assim, o bloqueio do TNF poderia ser prejudicial, aumentando a virulência amebiana. Descreve-se o caso de uma mulher de 46 anos com espondiloartrite que apresentou uma perfuração do colo por colite amebiana invasiva durante uso de anti-TNF.

  8. Risk factors for tuberculosis in inflammatory bowel disease: anti-tumor necrosis factor and hospitalization

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    Sabino Riestra

    Full Text Available Aims: To determine risk factors for active tuberculosis in patients with inflammatory bowel diseases. Methods: Retrospective, case-control study at 4 referral hospitals in Spain. Cases developed tuberculosis after a diagnosis of inflammatory bowel disease. Controls were inflammatory bowel disease patients who did not develop tuberculosis. For each case, we randomly selected 3 controls matched for sex, age (within 5 years and time of inflammatory bowel disease diagnosis (within 3 years. Inflammatory bowel disease characteristics, candidate risk factors for tuberculosis and information about the tuberculosis episode were recorded. Multivariate analysis and a Chi-squared automatic interaction detector were used. Results: Thirty-four cases and 102 controls were included. Nine of the 34 cases developed active tuberculosis between 1989 and 1999, and 25 became ill between 2000 and 2012. Multivariate regression showed an association between active tuberculosis and anti-TNF (tumor necrosis factor therapy in the previous 12 months (OR 7.45; 95% CI, 2.39-23.12; p = 0.001; hospitalization in the previous 6 months (OR 4.38; 95% CI, 1.18-16.20; p = 0.027; and albumin levels (OR 0.88; 95% CI, 0.81-0.95; p = 0.001. The median time between the start of biologic therapy and the onset of active tuberculosis was 13 (interquartile range, 1-58 months. Tuberculosis developed after a year of anti-TNF therapy in 53%, and late reactivation occurred in at least 3 of 8 patients. Conclusions: The main risks factors for developing tuberculosis were anti-TNF therapy and hospitalization. Over half the cases related to anti-TNF treatment occurred after a year.

  9. Golimumab and certolizumab: The two new anti-tumor necrosis factor kids on the block

    Directory of Open Access Journals (Sweden)

    Mittal Mohit

    2010-01-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF agents have revolutionized treatment of psoriasis and many other inflammatory diseases of autoimmune origin. They have considerable advantages over the existing immunomodulators. Anti-TNF agents are designed to target a very specific component of the immune-mediated inflammatory cascades. Thus, they have lower risks of systemic side-effects. In a brief period of 10 years, a growing number of biological therapies are entering the clinical arena while many more biologicals remain on the horizon. With time, the long-term side-effects and efficacies of these individual agents will become clearer and help to determine which ones are the most suitable for long-term care. Golimumab (a human monoclonal anti-TNF-α antibody and Certolizumab (a PEGylated Fab fragment of humanized monoclonal TNF-α antibody are the two latest additions to the anti-TNF regimen. Here, we are providing a brief description about these two drugs and their uses.

  10. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy

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    Beatriz Fernández-Vega

    2016-03-01

    Full Text Available Aims: To report a case of wet age-related macular degeneration (wet-AMD refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α drug, for concomitant Crohn's disease. Methods: Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment. Best-corrected visual acuity (BCVA was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT. Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results: A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg for a period of 40 months with intervals of 1-6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks. During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions: We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes.

  11. Drug immunogenicity in patients with inflammatory arthritis and secondary failure to tumour necrosis factor inhibitor therapies: the REASON study.

    Science.gov (United States)

    Balsa, Alejandro; Sanmarti, Raimon; Rosas, José; Martin, Victor; Cabez, Ana; Gómez, Susana; Montoro, María

    2018-04-01

    The aims were to evaluate the prevalence of anti-drug antibodies (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF therapy and to correlate ADA presence with anti-TNF concentration and clinical response. This was a cross-sectional, observational study of patients with active RA or SpA experiencing secondary failure to etanercept (ETN), infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were permitted. Serum anti-TNF and ADA levels were measured with two-site ELISA. Among 570 evaluable patients, those with RA (n = 276) were mostly female (80 vs 39%), older (56 vs 48 years), received concomitant DMARDs (83 vs 47%) and had maintained good clinical disease control for longer (202 vs 170 weeks) compared with patients with SpA (n = 294). ADA were found in 114/570 (20.0%) patients; 51/188 (27.1%) against INF and 63/217 (29.0%) against ADL; none against ETN. Of these 114 patients, 92 (81%) had no detectable serum drug concentrations. Proportionately more patients with SpA (31.3%) had anti-INF antibodies than those with RA (21.1%; P = 0.014). A significantly lower proportion of patients receiving concomitant DMARDs (16.5%) developed ADA than those on monotherapy (26.4%; P reasons for secondary treatment failure, but not the only one. Further investigations are needed to determine other causes of anti-TNF failure.

  12. Severe glandular tularemia in a patient treated with anti-tumour necrosis factor for psoriatic arthritis.

    Science.gov (United States)

    Calin, Ruxandra; Caumes, Eric; Reibel, Florence; Ali Mohamed, Anzime; Brossier, Florence; Foltz, Violaine; Boussouar, Samia; Fautrel, Bruno; Maurin, Max; Katlama, Christine; Pourcher, Valérie

    2017-07-01

    A case of severe glandular tularemia in a patient receiving anti-tumour necrosis factor (TNF) therapy is reported here. The patient required prolonged treatment with doxycycline-ciprofloxacin due to early relapse after ciprofloxacin was stopped. Tularemia may have a more severe course in patients receiving anti-TNF. This may thus be an indication for more aggressive treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Ultrasound Elasticity Imaging Predicts Therapeutic Outcomes of Patients With Crohn's Disease Treated With Anti-Tumour Necrosis Factor Antibodies.

    Science.gov (United States)

    Orlando, Stefania; Fraquelli, Mirella; Coletta, Marina; Branchi, Federica; Magarotto, Andrea; Conti, Clara Benedetta; Mazza, Stefano; Conte, Dario; Basilisco, Guido; Caprioli, Flavio

    2018-01-05

    Ultrasound elasticity imaging is a non-invasive technique developed to evaluate fibrosis. Measuring tissue strain by ultrasound elasticity imaging can reliably detect severe ileal fibrosis in patients with Crohn's disease [CD]. We have hypothesised that a more severe range of fibrosis might influence the therapeutic response to anti-tumour necrosis factor [TNF] treatment. The aim of this study was to assess the ability of ultrasound elasticity imaging to predict the therapeutic outcome for CD patients. Consecutive patients with ileal/ileocolonic CD, starting anti-TNF treatment, were enrolled for the study. These patients underwent bowel ultrasound and ultrasound elasticity imaging at baseline and at 14 and 52 weeks after anti-TNF treatment. Bowel wall stiffness was quantified by calculating the strain ratio between the mesenteric tissue and the bowel wall. Strain ratio ≥ 2 was used to identify severe ileal fibrosis. Transmural healing at 14 and 52 weeks was defined as bowel wall thickness ≤ 3 mm. Thirty patients with CD were enrolled. Five patients underwent surgery for bowel obstruction. The frequency of surgeries was significantly greater in patients with a strain ratio ≥ 2 at baseline [p = 0.003]. A significant reduction of the bowel thickness was observed after 14 and 52 weeks of anti-TNF treatment [p < 0.005]. A significant inverse correlation was observed between the strain ratio values at baseline and the thickness variations following anti-TNF therapy [p = 0.007]; 27% of patients achieved transmural healing at 14 weeks. The baseline strain ratio was significantly lower in patients with transmural healing [p < 0.05]. This study shows that ultrasound elasticity imaging predicts therapeutic outcomes for CD patients treated with anti-TNF. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  14. VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist.

    Science.gov (United States)

    Torrente-Segarra, Vicenç; Acosta Pereira, Asunción; Morla, Rosa; Ruiz, José Miguel; Clavaguera, Teresa; Figuls, Ramon; Corominas, Hector; Geli, Carme; Roselló, Rosa; de Agustín, Juan José; Alegre, Cayetano; Pérez, Carolina; García, Angel; Rodríguez de la Serna, Arturo

    to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  15. Certolizumab, an anti-TNF safe during pregancy? The CRIB Study results: an interview with Professor Xavier Mariette.

    Science.gov (United States)

    Mariette, Xavier

    2017-09-01

    Professor Xavier Mariette, MD, PhD, has served as the Head of the Rheumatology Department of Bicêtre Hospital, Paris-Sud University since 1999, a role he took following 10 years of practice of clinical immunology. Professor Mariette has initiated a number of clinical research studies on biotherapies in autoimmune diseases. He is the head of the French RATIO (Research Axed on Tolerance of Biotherapy) observatory, collecting specific rare serious adverse events in patients treated with anti-TNF. He initiated the French AIR (Autoimmunity and Rituximab) and ORA (Orencia and Rheumatoid arthritis) registries of patients with autoimmune diseases treated with rituximab and abatacept. He initiated clinical trials in Sjögren's syndrome with infliximab, hydroxychloroquine and belimumab. Professor Mariette is involved in basic research, leading a group working on pathogeny of Sjögren's syndrome, relationships between innate immunity and B-cell activation in autoimmunity and the relationships between autoimmunity and lymphoma. Professor Mariette is also very interested in new ways of teaching. In 2007, he participated with other European Experts in the creation of the EULAR Web Course of Rheumatology in 2007. Professor Mariette has been the President of the Scientific Committee of the EULAR meeting, which took place in Berlin in 2012 and is in 2016 the elect Chair of the EULAR standing committee on investigative rheumatology. Professor Mariette is co-author of more than 430 publications referenced in PubMed with an H-index of 61.

  16. Optimizing biological therapy in Crohn's disease.

    Science.gov (United States)

    Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

    2016-01-01

    Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

  17. Cerebral tuberculoma in a patient receiving anti-TNF alpha (adalimumab) treatment.

    LENUS (Irish Health Repository)

    Lynch, Karen

    2010-10-01

    We report a case of a cerebral tuberculoma in a 60-year-old woman with rheumatoid arthritis while receiving the anti-tumor necrosis factor alpha monoclonal antibody, adalimumab (Humira), for active disease. MR brain imaging for dyspraxia revealed a left parietal ring-enhancing lesion, which on resection was shown to be a necrotizing granuloma. There were no associated pulmonary lesions, and the patient was systemically well. Sputum and urine cultures were negative for tuberculosis. The patient was treated with anti-tuberculous medications and made an excellent recovery. We consider this to be the first documented case of tuberculosis involving the central nervous system occurring in the setting of adalimumab treatment.

  18. Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflammatory arthritis

    LENUS (Irish Health Repository)

    Biniecka, Monika

    2011-07-25

    Abstract Introduction To examine the effects of tumour necrosis factor (TNF) blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. Methods Eighteen inflammatory arthritis patients underwent synovial tissue oxygen (tpO2) measurements and clinical assessment of disease activity (DAS28-CRP) at baseline (T0) and three months (T3) after starting biologic therapy. Synovial tissue lipid peroxidation (4-HNE), T and B cell specific markers and synovial vascular endothelial growth factor (VEGF) were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA (mtDNA) mutations were assessed using Random Mutation Capture (RMC) assay. Results 4-HNE levels pre\\/post anti TNFtherapy were inversely correlated with in vivo tpO2 (P < 0.008; r = -0.60). Biologic therapy responders showed a significantly reduced 4-HNE expression (P < 0.05). High 4-HNE expression correlated with high DAS28-CRP (P = 0.02; r = 0.53), tender joint count for 28 joints (TJC-28) (P = 0.03; r = 0.49), swollen joint count for 28 joints (SJC-28) (P = 0.03; r = 0.50) and visual analogue scale (VAS) (P = 0.04; r = 0.48). Strong positive association was found between the number of 4-HNE positive cells and CD4+ cells (P = 0.04; r = 0.60), CD8+ cells (P = 0.001; r = 0.70), CD20+ cells (P = 0.04; r = 0.68), CD68+ cells (P = 0.04; r = 0.47) and synovial VEGF expression (P = 0.01; r = 063). In patients whose in vivo tpO2 levels improved post treatment, significant reduction in mtDNA mutations and DAS28-CRP was observed (P < 0.05). In contrast in those patients whose tpO2 levels remained the same or reduced at T3, no significant changes for mtDNA mutations and DAS28-CRP were found. Conclusions High levels of synovial oxidative stress and mitochondrial mutation burden are strongly associated with low in vivo oxygen tension and synovial inflammation. Furthermore these significant mitochondrial genome alterations are rescued following successful anti TNF

  19. Multimodal treatment of perianal fistulas in Crohn's disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial.

    LENUS (Irish Health Repository)

    de Groof, E Joline

    2015-08-20

    Currently there is no guideline for the treatment of patients with Crohn\\'s disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs.

  20. Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis.

    Science.gov (United States)

    Youngstein, Taryn; Peters, James E; Hamdulay, Shahir S; Mewar, Devesh; Price-Forbes, Alec; Lloyd, Mark; Jeffery, Rachel; Kinderlerer, Anne R; Mason, Justin C

    2014-01-01

    We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease. Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated. Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNFtherapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs. We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.

  1. Pharmacological therapy of spondyloarthritis.

    Science.gov (United States)

    Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

    2015-01-01

    The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

  2. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification.

    Science.gov (United States)

    Seto, Wai-Kay

    2015-04-28

    Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.

  3. Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: a patient perspective

    Directory of Open Access Journals (Sweden)

    Bolge SC

    2015-01-01

    Full Text Available Susan C Bolge,1 Amir Goren,2 Neeta Tandon1 1Health Economics and Outcomes Research, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 2Health Outcomes Practice, Kantar Health, New York, NY, USA Objective: To examine reasons why rheumatoid arthritis patients discontinued subcutaneous (SQ anti-tumor necrosis factor (anti-TNF treatment in the past 12 months, so as to help inform successful, uninterrupted therapy.Methods: Data were collected in March and April 2011 using self-reported, internet-based questionnaires. Study inclusion criteria comprised: rheumatoid arthritis diagnosis; discontinuation of SQ anti-TNF medication (adalimumab, certolizumab, etanercept, or golimumab within the past 12 months; aged ≥18 years; United States residency; and consent to participate. Patients reported primary and other reasons for discontinuation of their most recently discontinued anti-TNF.Results: Questionnaires from 250 patients were analyzed; 72.8% were female, 80.8% were white, and median age was 51 years. Patients had discontinued etanercept (n=109, adalimumab (n=98, certolizumab (n=24, or golimumab (n=19 within the past 12 months. When prompted about their primary reason for discontinuation, lack of effectiveness (40.8% was cited most often, followed by injection experience (18.4%. Combining prompted primary and other reasons for discontinuation, 60.8% of patients reported lack of effectiveness, while 40.8% reported injection experience, which included: pain/burning/discomfort after injection (14.4%; pain/burning/discomfort during injection (13.2%; injection reactions such as redness/swelling after injection (12.4%; dislike of self-injection (11.6%; dislike of frequency of injection (10.4%; and fear of injection/needles (6.8%. Conclusion: From the patient perspective, there are unmet needs with regard to the effectiveness and injection experience associated with SQ anti-TNF medications, which may lead to discontinuation. Treatment options with a

  4. Risk factor management: antiatherogenic therapies.

    Science.gov (United States)

    Gielen, Stephan; Sandri, Marcus; Schuler, Gerhard; Teupser, Daniel

    2009-08-01

    Despite the advances in interventional techniques, the management of stable atherosclerosis remains the domain of optimal guideline-oriented therapy. Recent studies on the effects of aggressive lipid lowering on atheroma volume changes using intravascular ultrasound indicate that it is possible to achieve atherosclerosis regression by reaching low-density lipoprotein (LDL) levels less than 75 mg/dl. The pleiotropic anti-inflammatory effects of statins contribute to the reduction of cardiovascular (CV) event observed with aggressive lipid lowering. As a second important strategy to prevent disease progression, lifestyle changes with regular physical exercise are capable of halting the atherosclerotic process and reducing angina symptoms and CV events. Optimal medical therapy, a healthy lifestyle with regular physical exercise, and coronary interventions are not mutually exclusive treatment strategies. Over the last few decades, both have proved to be effective in significantly reducing the CV mortality in the Western world. However, risk factor modification contributed to at least half the effect in the reduction of CV mortality. This figure provides an estimate of what could be achieved if we were to take risk factor modification more seriously - especially in the acute care setting. The knowledge is there: today we have a better understanding on how to stop progression and even induce regression of atherosclerosis. Much research still needs to be done and will be done. In the meantime, however, our primary focus should lie in implementing what is already known. In addition, it is essential not just to treat CV risk factors, but also to treat them to achieve the target values as set by the guidelines of European Society of Cardiology.

  5. Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

    Science.gov (United States)

    Feletar, Marie; Hall, Stephen; Bird, Paul

    2016-01-01

    To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

  6. The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region

    NARCIS (Netherlands)

    van Schie, K. A.; Hart, M. H.; de Groot, E. R.; Kruithof, S.; Aarden, L. A.; Wolbink, G. J.; Rispens, T.

    2015-01-01

    In a subset of patients, anti tumour necrosis factor (TNF) therapeutic antibodies are immunogenic, resulting in the formation of antidrug antibodies (ADAs). Neutralising ADAs compete with TNF for its binding site and reduces the effective serum concentration, causing clinical non-response. It is

  7. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model

    NARCIS (Netherlands)

    Wildenberg, Manon E.; Levin, Alon D.; Ceroni, Alessandro; Guo, Zhen; Koelink, Pim J.; Hakvoort, Theodorus B. M.; Westera, Liset; Bloemendaal, Felicia M.; Brandse, Johannan F.; Simmons, Alison; D'Haens, Geert R.; Ebner, Daniel; van den Brink, Gijs R.

    2017-01-01

    Background and Aims: Regulatory macrophages play a critical role in tissue repair, and we have previously shown that anti-tumour necrosis factor [TNF] antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the

  8. Therapeutic potential of combined anti-IL-1β IgY and anti-TNF-α IgY in guinea pigs with allergic rhinitis induced by ovalbumin.

    Science.gov (United States)

    Guo-Zhu, Hu; Xi-Ling, Zhu; Zhu, Wen; Li-Hua, Wu; Dan, He; Xiao-Mu, Wu; Wen-Yun, Zhou; Wei-Xu, Hu

    2015-03-01

    We have previously demonstrated that anti-IL-1β immunoglobulin yolk(IgY) inhibits pathological responses in allergic asthma guinea pigs induced by ovalbumin(OVA). This study aims to determine whether the combined blockade of IL-1β and TNF-α can more effectively inhibit allergic inflammation in allergic rhinitis(AR) guinea pigs induced by OVA. Healthy guinea pigs treated with saline were used as the healthy control. The AR guinea pigs induced by OVA were randomly divided into (1) the AR model group containing negative control animals treated with intranasal saline; (2) the 0.1% non-specific IgY treatment group treated with non-specific IgY; (3) the 0.1% anti-TNF-α IgY treatment group treated with 0.1% anti-TNF-α IgY; (4) the 0.1% anti-IL-1β IgY treatment group treated with 0.1% anti-IL-1β IgY; (5) the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group treated with 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY; and (6) the fluticasone propionate treatment group treated with fluticasone propionate. Cytokines were measured using an enzyme-linked immunosorbent assay. The results showed that IL-1β, IL-5, IL-9, IL-13, IL-18, IL-22, IL-33, TNF-α, TGF-β1 and OVA-specific IgE levels in the peripheral blood (PB) and nasal lavage fluid (NLF) significantly decreased at 2h, 4h or 8h in the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group compared to the AR model group and the 0.1% non-specific IgY treatment group (P<0.05). The data suggest that blockade of IL-1β and TNF-α by intranasal instillation of combined anti-IL-1β IgY and anti-TNF-α IgY could be a potential alternative strategy for preventing and treating allergic rhinitis. Copyright © 2014. Published by Elsevier B.V.

  9. Análise sistemática da influência do antifator de necrose tumoral [anti-TNF] sobre as taxas de infecção em pacientes com artrite reumatoide

    Directory of Open Access Journals (Sweden)

    Leslie Goh

    2013-12-01

    Full Text Available OBJETIVO: O presente trabalho tem como objetivo fornecer uma análise sistemática da influência do anti-TNF sobre as taxas de infecção em pacientes com artrite reumatoide (AR. MÉTODO: Pesquisamos na Medline para obter informações de controle de qualidade sobre as taxas de infecção em pacientes com AR tratados com anti-TNF. RESULTADOS: Atualmente, uma proporção elevada de pacientes com AR é usuária de agentes anti-TNF. Dados de registros nacionais em países da Europa de pacientes com AR tratados com anti-TNF sugerem que terapias biológicas estão intimamente ligadas à sepse. Apesar de estudos anteriores terem relatado um maior risco de infecções, atualmente há dados emergentes com maior duração de acompanhamento que sugerem um risco ajustado de 1,2. Os pacientes idosos e os com doença de longa data poderão apresentar uma taxa mais elevada de infecções graves em comparação às suas contrapartes mais novas com doença inicial. Hoje, há dados emergentes que sugerem que a terapia com anti-TNF está associada ao desenvolvimento de neutropenia logo após o início do tratamento. Os registros biológicos constataram que os pacientes com ARES tratados com anticorpos monoclonais apresentam aumento no risco de tuberculose (TB, em comparação aos tratados com bloqueadores dos receptores de TNF. Esse risco de infecção precisa ser ponderado em relação aos benefícios estabelecidos dos bloqueadores de TNF. CONCLUSÃO: A evidência atual sugere que o tratamento com anti-TNF na AR está intimamente associado à infecção. Os pacientes precisam estar cientes do risco de infecção, assim como dos benefícios estabelecidos dos bloqueadores de TNF, para que possam fornecer o consentimento informado para o tratamento.

  10. Effectiveness of anti-tumour necrosis factortherapy in Danish patients with inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bank, Steffen; Andersen, Paal Skytt; Burisch, Johan

    2015-01-01

    Introduction: The objective of this study was to evaluate the outcome of anti-tumour necrosis factor-α (anti-TNF) treatment in a large cohort of patients with inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) in clinical practice and to establish a cohort...... in clinical trials. Funding: The work was funded by Health Research Fund of Central Denmark Region, Colitis-Crohn Foreningen and the University of Aarhus (PhD grant). Trial registration: Clinicaltrials NCT02322008....

  11. Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

    Science.gov (United States)

    Kok, Beverley; Lester, Erica L W; Lee, William M; Hanje, A James; Stravitz, R Todd; Girgis, Safwat; Patel, Vaishali; Peck, Joshua R; Esber, Christopher; Karvellas, Constantine J

    2018-03-21

    Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

  12. The future role of anti-tumour necrosis factor (TNF) products in the treatment of rheumatoid arthritis.

    Science.gov (United States)

    Camussi, G; Lupia, E

    1998-05-01

    Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNF alpha a potential target for anticytokine therapy. Experimental studies have shown that TNF alpha blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNF alpha antibodies or soluble receptors have suggested a potential beneficial effect of TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNF alpha therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNF alpha therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNF alpha production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNF alpha

  13. Effects of anti-TNF-α treatment on lipid profile in rheumatic diseases: an analytical cohort study.

    Science.gov (United States)

    Hassan, Shadi; Milman, Uzi; Feld, Joy; Eder, Lihi; Lavi, Idit; Cohen, Shai; Zisman, Devy

    2016-11-10

    The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-α) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients. A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-α inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0-6, 6-12, 12-18, and 18-24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results. The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-α inhibitors, from 180.85 ± 2.12 mg/dl and 116.00 ± 3.55 mg/dl at baseline to 188.12 ± 2.35 mg/dl (p = 0.02) and 132.02 ± 4.63 mg/dl at 0-6 months (p < 0.01), respectively, and to 184.88 ± 2.09 mg/dl (p = 0.02) and 129.36 ± 4.32 mg/dl at 18-24 months (p < 0.01), respectively. AI increased following treatment with TNF-α inhibitors, from -0.032 ± 0.017 at baseline to 0.004 ± 0.019 at 18-24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 ± 2.86 mg/dl at baseline to 104.02 ± 3.57 mg/dl at 18-24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study. TNF-α inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.

  14. Ghrelin levels in patients with juvenile idiopathic arthritis: relation to anti-tumor necrosis factor treatment and disease activity.

    Science.gov (United States)

    Karagiozoglou-Lampoudi, Thomais; Trachana, Maria; Agakidis, Charalampos; Pratsidou-Gertsi, Polyxeni; Taparkou, Anna; Lampoudi, Sotiria; Kanakoudi-Tsakalidou, Florentia

    2011-10-01

    Studies in adults with rheumatoid arthritis reported low serum ghrelin that increased following anti-tumor necrosis factor (TNF) infusion. Data on juvenile idiopathic arthritis (JIA) are lacking. The aim of this pilot study was to explore serum ghrelin levels in patients with JIA and the possible association with anti-TNF treatment, disease activity, and nutritional status. Fifty-two patients with JIA (14/52 on anti-TNF treatment) were studied. Juvenile idiopathic arthritis was inactive in 3 of 14 anti-TNF-treated patients and in 11 of 38 non-anti-TNF-treated patients. The nutritional status, energy intake/requirements, appetite, and fasting serum ghrelin levels were assessed. Ghrelin control values were obtained from 50 individuals with minor illness matched for age, sex, and body mass index. Ghrelin levels in patients with JIA were significantly lower than in controls (P ghrelin levels were comparable to control values only in 3 patients with anti-TNF-induced remission. Ghrelin in non-anti-TNF-treated patients in remission was low. Multiple regression analysis showed that disease activity (P = .002, CI = -84.16 to -20.01) and anti-TNF treatment (P = .003, CI = -82.51 to -18.33) were significant independent predictors of ghrelin after adjusting for other potential confounders. Ghrelin did not correlate with nutritional status, energy balance, and appetite. Serum ghrelin is low in patients with JIA and is restored to values similar to those in controls following anti-TNF-induced remission. Our study provides evidence that TNF blockade is independently associated with serum ghrelin, which possibly contributes to anti-TNF-induced remission. These preliminary results could form the basis for future research. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Adverse events of anti-tumor necrosis factor α therapy in ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Qiang Tong

    Full Text Available This study aims to investigate the prevalence of short-term and long-term adverse events associated with tumor necrosis factor-α (TNF-α blocker treatment in Chinese Han patients suffering from ankylosing spondylitis (AS.The study included 402 Chinese Han AS patients treated with TNF-α blockers. Baseline data was collected. All patients were monitored for adverse events 2 hours following administration. Long-term treatment was evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF-α blockers.Short-term adverse events occurred in 20.15% (81/402, including rash (3.5%; 14/402, pruritus (1.2%; 5/402, nausea (2.2%; 9/402, headache (0.7%; 3/402, skin allergies (4.0%; 16/402, fever (0.5%; 2/402, palpitations (3.0%; 12/402, dyspnea (0.5%; 2/402, chest pain (0.2%; 1/402, [corrected] abdominal pain (1.0%; 4/402, hypertension (2.2%; 9/402, papilledema (0.5%; 2/402, laryngeal edema (0.2%; 1/402 and premature ventricular contraction (0.2%; 1/402. Long-term adverse events occurred in 59 (34.3%; 59/172 patients, including pneumonia (7.6%; 13/172, urinary tract infections (9.9%; 17/172, otitis media (4.7%; 8/172, tuberculosis are (3.5%; 6/172 [corrected], abscess (1.2%; 2/172, oral candidiasis (0.6%; 1/172, elevation of transaminase (1.7%; 3/172, anemia (1.2%; 2/172, hematuresis (0.6%; 1/172, constipation (2.3%; 4/172, weight loss (0.6%; 1/172, exfoliative dermatitis (0.6%; 1/172. CRP, ESR and disease duration were found to be associated with an increased risk of immediate and long-term adverse events (P<0.05. Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc (P<0.01.This study reports on the prevalence of adverse events in short-term and long-term treatment with TNF-α blocker monotherapy in Chinese Han AS patients. Duration of disease, erythrocyte sedimentation rate, and c-reactive protein serum levels were found to be associated with increased adverse events with anti-TNFtherapy. Long

  16. Cancer risk of anti-TNF-α at recommended doses in adult rheumatoid arthritis: a meta-analysis with intention to treat and per protocol analyses.

    Directory of Open Access Journals (Sweden)

    Guillaume Moulis

    Full Text Available BACKGROUND: The risk of malignancies on TNF-α antagonists is controversial. The aim of this survey was to assess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, including the five marketed drugs (infliximab, etanercept, adalimumab, golimumab and certolizumab used in line with the New Drug Application. Furthermore, the relative interest of modified intention to treat or per protocol analyses to assess such sparse events remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Data sources were MEDLINE, CENTRAL, ISI Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the drugs leading to their marketing approval, and clinicaltrials.gov, until 31 December 2012.We selected double-blind randomized controlled trials in adult rheumatoid arthritis patients, including at least one treatment arm in line with New Drug Application. We performed random effect meta-analysis, with modified intention to treat and per protocol analyses. Thirty-three trials were included. There was no excess risk of malignancies on anti-TNF-α administered in line with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59-1.44], as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82-1.98]. There was a non-significant tendency for an excess non-melanoma skin cancer risk in both models (respectively, 1.37 [0.71-2.66] and 1.90 [0.98-3.67]. With fixed effect Peto model restricting to trials during at least 52 weeks, the overall cancer risk was respectively 1.60 [0.97-2.64] and 1.22 [0.72-2.08]. Whatever the model, modified intention to treat analysis led to higher estimations than per protocol analysis. The later may underestimate the treatment effect when assessing very sparse events and when many patients dropped out in placebo arms. In metaregression, there was no differential risk among the five drugs. CONCLUSIONS/SIGNIFICANCE: This study did not find any evidence for an excess cancer risk on TNF

  17. Expression of soluble CD83 in plasma from early-stage rheumatoid arthritis patients is not modified by anti-TNF-alpha therapy

    DEFF Research Database (Denmark)

    Kristensen, Anne-Mette; Stengaard-Pedersen, Kristian; Hetland, Merete Lund

    2017-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases. In RA...... higher in synovial fluid than in plasma, and only a limited amount of membrane bound CD83 expression was detected on the surface of cells from peripheral blood and synovial fluid. Finally, confocal microscopy of RA synovial membranes revealed that CD83 was mainly localized intracellularly in a group...

  18. Macrophage Polarization and Utility of in Vivo Therapy with a Brain-Permeable Anti-TNF Agent in Models of Autism

    Science.gov (United States)

    2017-10-01

    plan to use. We began work on Aim 4 because it did not involve use of transgenic mouse colonies and pharmacological studies are underway to...the role of TNF genetically. But we will still have the pharmacological intervention with XPro1595 which is the more translational path forward...7/1/16-6/30/21 $497,000.00 Direct Costs “CSF, MRI , and PET biomarkers of neuroinflammation in

  19. Importancia del escrutinio para tuberculosis previo a la administración de agentes anti-TNF-α en uveítis: a propósito de un caso clínico

    Directory of Open Access Journals (Sweden)

    Enrique Leopoldo Zaldívar-Orta

    2014-10-01

    Conclusión: Es indispensable realizar pruebas de escrutinio para tuberculosis latente antes de iniciar tratamiento con agentes biológicos anti-TNF-α, particularmente con infliximab. Las pruebas que miden la producción de interferón gamma (IFN-γ in vitro en respuesta a los antígenos tuberculosos son una alternativa a la prueba cutánea clásica con tuberculina (PPD en la detección de tuberculosis, particularmente en individuos vacunados con el bacilo de Calmette-Guérin (BCG.

  20. Influencia de polimorfismos genéticos, variables analíticas y ambientales en las concentraciones valle de terapia anti-TNF de pacientes con enfermedad inflamatoria intestinal

    OpenAIRE

    Romero Cara, Patricia

    2015-01-01

    OBJETIVOS La terapia anti-TNF-alfa está indicada en el tratamiento de las enfermedades inflamatorias crónicas. Cuando la respuesta es inadecuada se recomienda la intensificación de la dosis. Sin embargo, ni las razones para esta recomendación, ni los múltiples mecanismos implicados son bien conocidos. Nuestro objetivo principal es investigar si polimorfismos en los genes FCGRT, FCGR2A y FCGR3A (relacionados con el metabolismo y eliminación de inmunoglobulinas) ejercen una influencia en la ...

  1. Down-regulation of the Th1, Th17, and Th22 pathways due to anti-TNF-α treatment in psoriasis.

    Science.gov (United States)

    Luan, Li; Han, Shixin; Wang, Hua; Liu, Xiaoming

    2015-12-01

    Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis. To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response. This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α). At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines. The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Pregnancy outcomes in women with inflammatory bowel disease following exposure to thiopurines and antitumor necrosis factor drugs: a systematic review with meta-analysis.

    Science.gov (United States)

    Mozaffari, S; Abdolghaffari, A H; Nikfar, S; Abdollahi, M

    2015-05-01

    Several studies have indicated the harmful effect of flare-up periods in pregnant women with inflammatory bowel disease (IBD) on their newborns. Therefore, an effective and safe medical treatment during pregnancy is of great concern in IBD patients. The aim of this study was to perform a meta-analysis on the outcomes of thiopurines use and a systematic review of antitumor necrosis factor (anti-TNF) drugs used during pregnancy in women with IBD. The results of cohorts evaluating the safety of anti-TNF drugs during pregnancy up to July 2013 were collected and analyzed. In the meta-analysis, a total of 312 pregnant women with IBD who used thiopurines were compared with 1149 controls (women with IBD who were not treated with any medication and women who were exposed to drugs other than thiopurines) to evaluate the drug effect on different pregnancy outcomes, including prematurity, low birth weight, congenital abnormalities, spontaneous abortion, and neonatal adverse outcomes. Results of statistical analysis demonstrated that congenital abnormalities were increased significantly in thiopurine-exposed group in comparison with control group who did not receive any medicine for IBD treatment. The summary odds ratio was 2.95 with 95% confidence interval = 1.03-8.43 (p = 0.04). We observed no significant differences in occurrence of other adverse pregnancy outcomes between compared groups. The results of cohorts evaluated the safety of anti-TNF drugs during pregnancy demonstrated no increase in occurrence of adverse pregnancy outcomes in comparison with controls except for the significant decrease in gestational age of newborns of drug-exposed mothers in one trial. In conclusion, a benefit-risk ratio should be considered in prescribing or continuing medicinal therapy during pregnancy of IBD patients. © The Author(s) 2014.

  3. Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

    Science.gov (United States)

    Umekita, Kunihiko; Umeki, Kazumi; Miyauchi, Shunichi; Ueno, Shiro; Kubo, Kazuyoshi; Kusumoto, Norio; Takajo, Ichiro; Nagatomo, Yasuhiro; Okayama, Akihiko

    2015-09-01

    Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

  4. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  5. Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin.

    Science.gov (United States)

    Chen, Chih-Yen; Tsai, Chang-Youh; Lee, Pui-Ching; Lee, Shou-Dong

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNFtherapy on body weight, appetite, plasma gut hormones and leptin have not been investigated. Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study). Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group. Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.

  6. Serum Concentration of Anti-TNF Antibodies, Adverse Effects and Quality of Life in Patients with Inflammatory Bowel Disease in Remission on Maintenance Treatment

    NARCIS (Netherlands)

    Brandse, Johannan F.; Vos, Laura M. C.; Jansen, Jeroen; Schakel, Toos; Ponsioen, Cyriel I. J.; van den Brink, Gijs R.; D'Haens, Geert R.; Löwenberg, Mark

    2015-01-01

    Background and aims: High serum concentrations of infliximab [IFX] and adalimumab [ADA] may be associated with adverse effects in patients with inflammatory bowel disease [IBD]. We aimed to investigate whether high anti-tumour necrosis factor [TNF] trough levels [TLs] were associated with toxicity

  7. Cardiovascular safety of biologic therapies for the treatment of RA.

    Science.gov (United States)

    Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

    2011-11-15

    Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

  8. Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bank, S; Andersen, P S; Burisch, J

    2014-01-01

    Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-T...... setting.The Pharmacogenomics Journal advance online publication, 29 April 2014; doi:10.1038/tpj.2014.19....

  9. Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis.

    Science.gov (United States)

    Alivernini, Stefano; Pugliese, Daniela; Tolusso, Barbara; Bui, Laura; Petricca, Luca; Guidi, Luisa; Mirone, Luisa; Rapaccini, Gian Ludovico; Federico, Francesco; Ferraccioli, Gianfranco; Armuzzi, Alessandro; Gremese, Elisa

    2018-01-01

    Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. Patients with IBD without history of coexisting joint involvement who developed arthritis under TNF-i were enrolled. Each patient underwent ST biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters (anticitrullinated peptides antibodies (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were enrolled as comparison. 10 patients with IBD (age 46.0±9.7 years, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-i exposure, six with Crohn's disease and four with ulcerative colitis, respectively) were studied. At ST level, IHC revealed that patients with IBD with paradoxical arthritis showed more similar histological findings in terms of synovial CD68 + , CD21 + , CD20 + , CD3 + and CD117 + cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, patients with IBD showed the presence of CD68 + , CD3 + , CD117 + and CD20 + cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of conventional disease-modifying antirheumatic drugs and switch to ustekinumab were more effective than swapping into different TNF-i in patients with IBD with paradoxical arthritis. Patients with IBD may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.

  10. Influencing factors of radioiodine therapy in hyperthyroidism in adults

    International Nuclear Information System (INIS)

    Xu Jiehua; Zhang Zikang; Cheng Muhua; Wu Chunxing; Wang Ping; Shan Hong

    2007-01-01

    The study was to evaluate factors affecting outcome of 131 I therapy in hyperthyroidism for optimizing the method. Data from 213 patients who received 131 I treatment from July 2003 to July 2005 in our department were retrospectively analyzed. Factors possibly contributing to the outcome of the 1311 therapy were analyzed, including gender, age, history of antithyroid drag, thyroid volume, duration of disease and radioactive iodine uptake rate. Multivariate analysis was done. The rates of euthyroidism and hypothyroidism were 69% and 8.5%, respectively, after one time 131 I therapy. Multivariate analysis of the patients showed no statistically significant factors affecting the outcome of 131 I therapy. The study showed that 131 I dose can be directly calculated, and this simplifies the dose-determined method and individualizes the therapy. (authors)

  11. Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK

    Directory of Open Access Journals (Sweden)

    Wilson MR

    2017-10-01

    Full Text Available Michele R Wilson,1 Ismail Azzabi Zouraq,2 Helene Chevrou-Severac,2 Ross Selby,3 Matthew C Kerrigan4 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Takeda Pharmaceuticals International AG, Zurich, Switzerland; 3Takeda UK Ltd., Bucks, UK; 4PHMR Limited, London, UK Objective: To examine the clinical and economic impact of vedolizumab compared with conventional therapy in the treatment of moderately-to-severely active ulcerative colitis (UC in the UK based on results of the GEMINI I trial. Methods: A decision-analytic model in Microsoft Excel was used to compare vedolizumab with conventional therapy (aminosalicylates, corticosteroids, immunomodulators for the treatment of patients with UC in the UK. We considered the following three populations: the overall intent-to-treat population from the GEMINI I trial, patients naïve to anti-TNF therapy, and those who had failed anti-TNF-therapy. Population characteristics and efficacy data were obtained from the GEMINI I trial. Other inputs (eg, unit costs, probability of surgery, mortality were obtained from published literature. Time horizon was a lifetime horizon, with costs and outcomes discounted by 3.5% per year. One-way and probabilistic sensitivity analyses were conducted to measure the impact of parameter uncertainty. Results: Vedolizumab had incremental cost-effectiveness ratios of £4,095/quality-adjusted life-year (QALY, £4,423/QALY, and £5,972/QALY compared with conventional therapy in the intent-to-treat, anti-TNF-naïve, and anti-TNF-failure populations, respectively. Patients on vedolizumab accrued more QALYs while incurring more costs than patients on conventional therapy. The sensitivity analyses showed that the results were most sensitive to induction response and transition probabilities for each treatment. Conclusion: The results suggest that vedolizumab results in more QALYs and may be a cost-effective treatment option compared with conventional therapy for both anti-TNF

  12. Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome

    DEFF Research Database (Denmark)

    Coenen, Marieke J H; Enevold, Christian; Barrera, Pilar

    2010-01-01

    Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication.......Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication....

  13. Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zhao, Xianda; Fan, Wei; Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

    2016-12-06

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.

  14. The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

    Science.gov (United States)

    Deitch, Iris; Amer, Radgonde; Tomkins-Netzer, Oren; Habot-Wilner, Zohar; Friling, Ronit; Neumann, Ron; Kramer, Michal

    2018-04-01

    This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.

  15. Tumor necrosis factor alpha polymorphism correlates with deleterious effects of ultraviolet B light on cutaneous immunity

    NARCIS (Netherlands)

    Vincek, V.; Kurimoto, I.; Medema, J. P.; Prieto, E.; Streilein, J. W.

    1993-01-01

    Intradermally injected tumor necrosis factor alpha (TNF-alpha) mimics the effects of UV B light (UVB) radiation and neutralizing anti-TNF-alpha antibodies abolish the deleterious effects of UVB on induction of contact hypersensitivity suggesting that TNF-alpha is the major mediator of UVB effects on

  16. Dose modification factors in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Allen, B.J. (Australian Nuclear Science and Technology Organization (ANSTO), Menai (Australia))

    1993-01-01

    The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes. (orig.).

  17. Uptake of isoniazid preventive therapy and its associated factors ...

    African Journals Online (AJOL)

    Background: Isoniazid Preventive Therapy (IPT) is an effective intervention for prevention of tuberculosis (TB) among HIV positive patients, and its use is recommended by the World Health Organization (WHO). Unfortunately the uptake of IPT in Kenya remains low (33%-40%) with limited knowledge on the factors that affect ...

  18. Factors related to pain during routine photodynamic therapy

    DEFF Research Database (Denmark)

    Miller, I M; Nielsen, J S; Lophaven, S

    2011-01-01

    between pain-reducing intervention and diagnosis, pre-treatment, gender or age was found. CONCLUSIONS: Pain-reducing intervention was required in 44% of the PDT treatments. Intervention was particularly required when treating lesions in areas suited for PDT therapy for cosmetic reasons such as the scalp......BACKGROUND: Pain may be a limiting factor in the use of photodynamic therapy (PDT). The consequences of the pain i.e. the resources spent on pain-intervention during routine PDT therapy are poorly described. OBJECTIVES: To describe the consequences of pain during PDT by describing the use of pain......-reducing interventions in routine use. We studied the frequency as well as level of pain-reducing intervention. METHODS: Descriptive data from PDT treated patients. The level of pain-reducing intervention was graded 0, no intervention; +, cold water spray and ++, pause or nerve block. RESULTS: Data from 983 PDT...

  19. Factoring nonviral gene therapy into a cure for hemophilia A.

    Science.gov (United States)

    Gabrovsky, Vanessa; Calos, Michele P

    2008-10-01

    Gene therapy for hemophilia A has fallen short of success despite several clinical trials conducted over the past decade. Challenges to its success include vector immunogenicity, insufficient transgene expression levels of Factor VIII, and inhibitor antibody formation. Gene therapy has been dominated by the use of viral vectors, as well as the immunogenic and oncogenic concerns that accompany these strategies. Because of the complexity of viral vectors, the development of nonviral DNA delivery methods may provide an efficient and safe alternative for the treatment of hemophilia A. New types of nonviral strategies, such as DNA integrating vectors, and the success of several nonviral animal studies, suggest that nonviral gene therapy has curative potential and justifies its clinical development.

  20. Factors associated with therapy noncompliance in type-2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Hernández-Ronquillo Lizbeth

    2003-01-01

    Full Text Available OBJECTIVE: To identify the frequency and factors associated with therapy noncompliance in type-2 diabetes mellitus patients. MATERIAL AND METHODS: A cross-sectional study was carried out in 79 patients with type-2 diabetes mellitus seen in major hospitals of Mexico City. Patients were visited at home, from March 1998 to August 1999, to measure compliance with prescribed therapy. Complying patients were defined as those taking at least 80% of their pills or 80% of their corresponding insulin dose. The degree of compliance with therapy components (diet, amount of exercise, and keeping appointments was measured. RESULTS: The average age of study subjects was 59 years (SD 11 years; 73% (n=58 were female subjects. The overall frequency of noncompliance was 39%. Noncompliance rates were: 62% for dietary recommendations, 85% for exercise, 17% for intake of oral hypoglycemic medication, 13% for insulin application, and 3% for appointment keeping. Hypertension plus obesity was the only factor significantly associated with noncompliance (OR 4.58, CI 95% 1.0, 22.4, p=0.02. CONCLUSIONS: The frequency of therapy noncompliance was very high, especially for diet and exercise.

  1. Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

    OpenAIRE

    Aldana Silva, Carolina; Chaparro Reyes, Laura Daniela

    2015-01-01

    Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y ...

  2. Radiological remission and recovery of thirst appreciation after infliximab therapy in adipsic diabetes insipidus secondary to neurosarcoidosis.

    Science.gov (United States)

    O'Reilly, M W; Sexton, D J; Dennedy, M C; Counihan, T J; Finucane, F M; O'Brien, T; O'Regan, A W

    2015-08-01

    Neurosarcoidosis is a rare and aggressive variant of systemic sarcoidosis which may result in hypothalamic-pituitary dysfunction. We report a case of hypothalamic hypopituitarism secondary to neurosarcoidosis complicated by adipsic diabetes insipidus (ADI). Initiation of anti-tumour necrosis factor-α (TNF-α) therapy resulted in both radiological disease remission and recovery of osmoregulated thirst appreciation after 3 months. A 22-year-old man was referred to the endocrinology service with profound weight gain, polyuria and lethargy. Biochemical testing confirmed anterior hypopituitarism while posterior pituitary failure was confirmed by hypotonic polyuria responding to desmopressin. Magnetic resonance imaging (MRI) demonstrated extensive hypothalamic infiltration; neurosarcoidosis was confirmed histologically after excisional cervical lymph node biopsy. Osmoregulated thirst appreciation was normal early in the disease course despite severe hypotonic polyuria. However, subsequent subjective loss of thirst appreciation and development of severe hypernatraemia in the setting of normal cognitive function indicated onset of ADI. Clinical management involved daily weighing, regular plasma sodium measurement, fixed daily fluid intake and oral desmopressin. We initiated immunosuppressive therapy with pulsed intravenous anti-TNFtherapy (infliximab) after multidisciplinary team consultation. Infliximab therapy resulted in successful radiological disease remission and complete recovery of osmoregulated thirst appreciation. This was confirmed by subjective return of thirst response and maintenance of plasma sodium in the normal range in the absence of close biochemical monitoring. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNFtherapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  4. Factors influencing radiation therapy student clinical placement satisfaction

    International Nuclear Information System (INIS)

    Bridge, Pete; Carmichael, Mary-Ann

    2014-01-01

    Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning

  5. Factors influencing radiation therapy student clinical placement satisfaction

    Science.gov (United States)

    Bridge, Pete; Carmichael, Mary-Ann

    2014-01-01

    Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning. PMID:26229635

  6. Factors influencing radiation therapy student clinical placement satisfaction

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Pete; Carmichael, Mary-Ann [School of Clinical Sciences, Queensland University of Technology, Brisbane (Australia)

    2014-02-15

    Introduction: Radiation therapy students at Queensland University of Technology (QUT) attend clinical placements at five different clinical departments with varying resources and support strategies. This study aimed to determine the relative availability and perceived importance of different factors affecting student support while on clinical placement. The purpose of the research was to inform development of future support mechanisms to enhance radiation therapy students’ experience on clinical placement. Methods: This study used anonymous Likert-style surveys to gather data from years 1 and 2 radiation therapy students from QUT and clinical educators from Queensland relating to availability and importance of support mechanisms during clinical placements in a semester. Results: The study findings demonstrated student satisfaction with clinical support and suggested that level of support on placement influenced student employment choices. Staff support was perceived as more important than physical resources; particularly access to a named mentor, a clinical educator and weekly formative feedback. Both students and educators highlighted the impact of time pressures. Conclusions: The support offered to radiation therapy students by clinical staff is more highly valued than physical resources or models of placement support. Protected time and acknowledgement of the importance of clinical education roles are both invaluable. Joint investment in mentor support by both universities and clinical departments is crucial for facilitation of effective clinical learning.

  7. Factors Associated With Academic Performance Among Second-Year Undergraduate Occupational Therapy Students

    OpenAIRE

    Bonsaksen, Tore; Ellingham, Brian; Carstensen, Tove

    2018-01-01

    Background: Research into occupational therapy education and its outcomes for students is growing. More research is needed to determine the factors of importance for occupational therapy students’ academic outcomes. This study aimed to investigate factors associated with academic performance among second-year undergraduate occupational therapy students in Norway. Methods: Occupational therapy students (n = 111) from two education programs completed questionnaires asking for sociodemograph...

  8. The physician's role in selecting a factor replacement therapy.

    Science.gov (United States)

    Pipe, S W

    2006-03-01

    Over the past 20 years, transmissions of human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus have been virtually eliminated from plasma-derived or recombinant therapy in the USA, a record that can be largely attributed to the use of effective screening and inactivation technologies for known pathogens. The next significant threat will likely come from the emergence of a new, blood-borne infectious disease, perhaps one transmitted by a non-lipid-enveloped virus or prion, for which current inactivation methods are ineffective. Following the HIV crisis of the 1980s, government, patient advocacy groups, medical and scientific communities and the manufacturers of clotting therapies can learn from the past and approach potential threats from emerging pathogens in a proactive and productive manner. For clinicians, this includes actively engaging patients in a dialogue about all the factors that may influence their choice of clotting factor therapies, including emerging pathogens, patient convenience, consistency and reliability of supply, relative cost/benefit ratios, reimbursement issues (where applicable), patient preference and brand loyalty. It is our obligation as healthcare providers to understand potential risks and help make proactive decisions with our patients, decisions that often must be made in an environment of scientific uncertainty. Threats from infectious agents that were once deemed theoretical can, and often do, ultimately become real, with serious implications for morbidity and mortality.

  9. Increased risk of post-operative complications in patients with Crohn’s disease treated with anti-tumour necrosis factor α agents - a systematic review

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa; Theede, Klaus; Olaison, Per Olov Gunnar

    2014-01-01

    INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

  10. Increased risk of post-operative complications in patients with Crohn's disease treated with anti-tumour necrosis factor α agents - a systematic review

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa; Theede, Klaus; Olaison, Gunnar

    2014-01-01

    INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

  11. Tumor Necrosis Factor-α is Associated with Positive Lymph Node Status in Patients with Recurrence of Colorectal Cancer – Indications for Anti-TNF-α Agents in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    M. Grimm

    2010-01-01

    Full Text Available Introduction: The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis.

  12. Factors predicting successful discontinuation of continuous renal replacement therapy.

    Science.gov (United States)

    Katayama, S; Uchino, S; Uji, M; Ohnuma, T; Namba, Y; Kawarazaki, H; Toki, N; Takeda, K; Yasuda, H; Izawa, J; Tokuhira, N; Nagata, I

    2016-07-01

    This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

  13. Risk factors and periimplantitis in implant therapy. Narrative review

    Directory of Open Access Journals (Sweden)

    Francis Bravo

    2013-12-01

    Full Text Available Diseases involving tissue around the teeth and osseointegrated implants are the result of an interaction between some type of pathological agent (bacterial, viral, etc. and host immune response. These interactions can occur both in the dental tissues as those biomaterials which are introduced to attempt to correct some type of periodontal disease, the implant being a biocompatible substitute of the teeth is not free from this type of interaction often enrolled periodontal and peri-implant pathology. The peri-implantitis is a type of disease that results from this interaction, the risk factors and risk indicators of peri-implantitis are broad and complex. This article summarizes the multiple sources of information in the scientific literature to address in detail the aspects of the main risk factors and the peri-implantitis in the peri implant therapy.

  14. Patient adherence to antihypertensive therapy and its individual psychological factors

    Directory of Open Access Journals (Sweden)

    Lidia Trachuk

    2016-09-01

    Full Text Available Background. In the treatment of chronic, especially asymptomatic pathology one of the main problem is the adherence to therapy. Patients with arterial hypertension need long-term, often lifelong medication, and how strictly they adhere to prescriptions often determines the course of the disease and the medical measures effectiveness. According to statistics, more than half of patients with hypertension are characterized by low compliance, which leads to complications of this disease. The objective of the research is to identify and analize the individual psychological factors that determine patient adherence to antihypertensive therapy. Methods and materials. This study was conducted during 2011-2013 at the cardiology departments of the Kyiv Alexander Hospital, polyclinics number 2 Shevchenko district in Kyiv, Desnyanskiy clinic №3 district in Kyiv, medical center "Adonis plus". We examined 203 patients with arterial hypertension (average age 53,5 ± 4,5 years. Methods: socio-demographic, clinical, clinical and psychological, psychodiagnostical, mathematical and statistical methods. Psychodiagnostical method included: 8-item Morisky medical adherence scale (Morisky D. E., 2008; self-assessment anxiety scale Charles D. Spielberger – Y.L Hanin (A.V. Batarshev, 2005; the Minnesota Multiphasic Personality Inventory questionnaire (MMRI (F.B. Berezin, 1994; "The level of subjective control" (A.A. Rean, 2001; "Index of attitudes to health" (S.D. Deryabo, VA Yasvin, 2000. Results. According to the results of 8-item Morisky medical adherence scale patients were divided into 3 groups according to the level of compliance - with high (26.11%, average (24.14% and low (49.75% levels of adherence to antihypertensive therapy. The individual-psychological predictors of poor adherence to antihypertensive therapy include the following personal characteristics of patients: a low level of intensity of attitude to health, internal type of subjective control, a

  15. Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.

    Science.gov (United States)

    Kobayashi, Tetsuo; Yokoyama, Tomoko; Ito, Satoshi; Kobayashi, Daisuke; Yamagata, Akira; Okada, Moe; Oofusa, Ken; Narita, Ichiei; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

    2014-11-01

    Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy. The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases. The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

  16. Placental growth factor expression is reversed by antivascular endothelial growth factor therapy under hypoxic conditions.

    Science.gov (United States)

    Zhou, Ai-Yi; Bai, Yu-Jing; Zhao, Min; Yu, Wen-Zhen; Huang, Lv-Zhen; Li, Xiao-Xin

    2014-08-01

    Clinical trials have revealed that the antivascular endothelial growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP). But the low level of VEGF was necessary as a survival signal in healthy conditions, and endogenous placental growth factor (PIGF) is redundant for development. The purpose of this study was to elucidate the PIGF expression under hypoxia as well as the influence of anti-VEGF therapy on PIGF. CoCl2-induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an in vivo study. The expression patterns of PIGF under hypoxic conditions and the influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse transcription-polymerase chain reaction (RTPCR). The retinal avascular areas and neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments were calculated. Retina PIGF concentration was evaluated by ELISA after treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated by proliferation and migration studies. PIGF mRNA expression was reduced by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However, PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and migration under normal conditions, but it stimulated cell proliferation and migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts in OIR mice (P<0.05). The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy.

  17. Down-titration and discontinuation strategies of tumor necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.

    Science.gov (United States)

    van Herwaarden, Noortje; den Broeder, Alfons A; Jacobs, Wilco; van der Maas, Aatke; Bijlsma, Johannes W J; van Vollenhoven, Ronald F; van den Bemt, Bart J F

    2014-09-29

    Anti-tumor necrosis factor (TNF) agents are effective in treating patients with rheumatoid arthritis (RA), but they are associated with (dose-dependent) adverse effects and high costs. To prevent overtreatment, several trials have assessed the effectiveness of down-titration compared with continuation of the standard dose. To evaluate the benefits and harms of down-titration (dose reduction, discontinuation or disease activity guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) on disease activity, functioning, costs, safety and radiographic damage compared with usual care in patients with RA and low disease activity. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8, 2013; Ovid MEDLINE (1946 to 8 September 2013); EMBASE (1947 to 8 September 2013); Science Citation Index (Web of Science); and conference proceedings of the American College of Rheumatology (2005 to 2012) and European League against Rheumatism (2005 to 2013). We contacted authors of the seven included studies to ask for additional information on their study; five responded. Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing down-titration (dose reduction, discontinuation, disease activity-guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) to usual care/no down-titration in patients with RA and a low disease activity state. Two review authors independently selected studies, assessed risk of bias and extracted data. Six RCTs and one CCT (total 1203 participants), reporting anti-TNF down-titration, were included. Three studies (559 participants) reported anti-TNF dose reduction compared with anti-TNF continuation. Five studies (732 participants) reported anti-TNF discontinuation compared with anti-TNF continuation (two studies assessed both anti-TNF discontinuation and dose reduction), and one study assessed disease activity

  18. Factors Affecting Hemodialysis Patients' Satisfaction with Their Dialysis Therapy

    Directory of Open Access Journals (Sweden)

    M. Al Eissa

    2010-01-01

    Full Text Available Aim. To assess the degree of satisfaction among hemodialysis patients and the factors influencing this satisfaction. Methods. Patients were recruited from 3 Saudi dialysis centers. Demographic data was collected. Using 1 to 10 Likert scale, the patients were asked to rate the overall satisfaction with, and the overall impact of, their dialysis therapy on their lives and to rate the effect of the dialysis therapy on 15 qualities of life domains. Results. 322 patients were recruited (72.6% of the total eligible patients. The mean age was 51.7 years (±15.4; 58% have been on dialysis for >3 years. The mean Charlson Comorbidity Index was 3.2 (±2, and Kt/V was 1.3 (±0.44. The mean satisfaction score was (7.41 ± 2.75 and the mean score of the impact of the dialysis on the patients' lives was 5.32 ± 2.55. Male patients reported worse effect of dialysis on family life, social life, energy, and appetite. Longer period since the commencement of dialysis was associated with adverse effect on finances and energy. Lower level of education was associated with worse dialysis effect on stress, overall health, sexual life, hobbies, and exercise ability. Conclusion. The level of satisfaction is affected by gender, duration on dialysis, educational level, and standard of care given.

  19. How do patients with inflammatory bowel disease want their biological therapy administered?

    Directory of Open Access Journals (Sweden)

    Lindsay Hannah

    2010-01-01

    Full Text Available Abstract Background Infliximab is usually administered by two monthly intravenous (iv infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn's Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration. The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD patients for two currently available anti-TNF agents and the reasons for their choices. Methods An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous were available, which drug route of administration would they choose. Results One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response. The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent preferred infliximab and 19 patients (24 percent preferred adalimumab (p = 0.07. Twenty-six patients (33 percent did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv was: "I do not like the idea of self-injecting," (67 percent. For those patients who preferred adalimumab (sc the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent. Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab six patients stated that they would prefer infliximab if given

  20. Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography.

    Science.gov (United States)

    Baraliakos, X; Heldmann, F; Callhoff, J; Listing, J; Appelboom, T; Brandt, J; Van den Bosch, F; Breban, M; Burmester, Gr; Dougados, M; Emery, P; Gaston, H; Grunke, M; Van Der Horst-Bruinsma, I E; Landewé, R; Leirisalo-Repo, M; Sieper, J; De Vlam, K; Pappas, D; Kiltz, U; Van Der Heijde, D; Braun, J

    2014-10-01

    To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS). CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation. In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years. Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'inflammation-FD-new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Wilms tumour: prognostic factors, staging, therapy and late effects

    International Nuclear Information System (INIS)

    Kaste, Sue C.; Dome, Jeffrey S.; Babyn, Paul S.; Graf, Norbert M.; Grundy, Paul; Godzinski, Jan; Levitt, Gill A.; Jenkinson, Helen

    2008-01-01

    Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale d'Oncologie Pediatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial development

  2. Wilms tumour: prognostic factors, staging, therapy and late effects

    Energy Technology Data Exchange (ETDEWEB)

    Kaste, Sue C. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Dome, Jeffrey S. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Babyn, Paul S. [Hospital for Sick Children, Department of Radiology, Toronto (Canada); Graf, Norbert M. [University Hospital of the Saarland, Clinic for Pediatric Oncology and Hematology, Homburg (Germany); Grundy, Paul [University of Alberta, Division of Pediatric Hematology, Oncology and Palliative Care, and Northern Alberta Children' s Cancer Program, Edmonton (Canada); Godzinski, Jan [Mother and Child Institute, Department of Oncological Surgery for Children and Adolescents, Warsaw (Poland); Levitt, Gill A. [Great Ormond Street Hospital for Sick Children NHS Trust, Paediatric Oncology, London (United Kingdom); Jenkinson, Helen [Birmingham Children' s Hospital NHS Trust, Oncology Department, Birmingham (United Kingdom)

    2008-01-15

    Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale d'Oncologie Pediatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial

  3. Factors associated with poor outcomes of continuous renal replacement therapy.

    Directory of Open Access Journals (Sweden)

    Chih-Chin Kao

    Full Text Available Continuous renal replacement therapy (CRRT is one of the dialysis modalities for critically ill patients. Despite intensive dialysis care, a high mortality rate is found in these patients. Our objective was to investigate the factors associated with poor outcomes in these patients. We conducted a retrospective cohort study using the National Health Insurance Research Database. Records of critically ill patients who received CRRT between 2007 and 2011 were retrieved, and the patients were categorized into two groups: those with acute kidney injury (AKI and those with history of end-stage renal disease (ESRD. Our primary and secondary outcomes were in-hospital mortality and long-term survival and non-renal recovery (long-term dialysis dependence, respectively, in the AKI group. We enrolled 15,453 patients, with 13,204 and 2249 in the AKI and ESRD groups, respectively. Overall, 66.5% patients died during hospitalization. In-hospital mortality did not differ significantly between groups (adjusted odds ratio, 0.93; 95% CI, 0.84-1.02. Age, chronic liver disease, and cancer history were identified as independent risk factors for in-hospital mortality in both groups. Hypertension was associated with higher risk of in-hospital mortality in patients with AKI. Age, coronary artery disease, and admission to the medical intensive care unit (MICU were risk factors for long-term dialysis dependence in patients with AKI. Patients with AKI and ESRD have similarly poor outcomes after CRRT. Older age and presence of chronic liver disease and cancer were associated with higher mortality. Older age, presence of coronary artery disease, and admission to MICU were associated with lower renal recovery rate in patients with AKI.

  4. Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Stimulating Factor in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Anastasia Makris

    2018-01-01

    Full Text Available ObjectivesGranulocyte monocyte colony-stimulating factor (GM-CSF is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA, despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies.MethodsIntracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+ and T (CD3+ cells from RA patients (n = 40, disease (n = 31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic rheumatic diseases n = 6 and healthy (n = 16 controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, n = 10 or anti-tumor necrosis factor (anti-TNF, n = 10 therapy.ResultsAmong untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89 an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2% and T (3.4 ± 1.6% cells was detected compared with both disease (1.7 ± 0.9%, p < 0.0001 and 1.7 ± 1.3%, p < 0.0001, respectively and healthy (0.3 ± 0.2%, p < 0.0001 and 0.6 ± 0.6%, p < 0.0001 controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, p = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, p < 0.0001, respectively and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, p < 0.0001 compared to GM-CSF− cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect.DiscussionThis is the first study showing an expanded population of GM-CSF+ B and T lymphocytes

  5. Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients.

    Science.gov (United States)

    Iborra, Marisa; Pérez-Gisbert, Javier; Bosca-Watts, Marta Maia; López-García, Alicia; García-Sánchez, Valle; López-Sanromán, Antonio; Hinojosa, Esther; Márquez, Lucía; García-López, Santiago; Chaparro, María; Aceituno, Montserrat; Calafat, Margalida; Guardiola, Jordi; Belloc, Blanca; Ber, Yolanda; Bujanda, Luis; Beltrán, Belén; Rodríguez-Gutiérrez, Cristina; Barrio, Jesús; Cabriada, José Luis; Rivero, Montserrat; Camargo, Raquel; van Domselaar, Manuel; Villoria, Albert; Schuterman, Hugo Salata; Hervás, David; Nos, Pilar

    2017-07-01

    Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA. This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response. We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission. In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.

  6. Factors associated with suboptimal adherence to antiretroviral therapy in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Li, Patrick CK; Phanuphak, Praphan; Sirisanthana, Thira; Sungkanuparph, Somnuek; Kantipong, Pacharee; Lee, Christopher KC; Mustafa, Mahiran; Merati, Tuti; Kamarulzaman, Adeeba; Singtoroj, Thida; Law, Matthew

    2014-01-01

    Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) 14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported 2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social

  7. Factors influencing cosmetic results after conservation therapy for breast cancer

    International Nuclear Information System (INIS)

    Taylor, Marie E.; Perez, Carlos A.; Halverson, Karen J.; Kuske, Robert R.; Philpott, Gordon W.; Garcia, Delia M.; Mortimer, Joanne E.; Myerson, Robert J.; Radford, Diane; Rush, Carol

    1995-01-01

    optimum dose distribution with compensating filters (p = 0.002). Daily fraction size of 1.8 Gy vs. 2.0 Gy, boost vs. no boost, type of boost (brachytherapy vs. electrons), total radiation dose, and use of bolus were not significant factors. Use of concomitant chemotherapy with irradiation impaired excellent cosmetic outcome (p = 0.02). Use of sequential chemotherapy or adjuvant tamoxifen did not appear to diminish excellent cosmetic outcomes (p = 0.31). Logistic regression for excellent cosmetic outcome analysis was completed for age, tumor size, menopausal status, race, type of surgery, volume of breast tissue resected, scar orientations, whole breast radiation dose, total radiation dose, number of radiation fields treated, and use of adjuvant chemotherapy. Significant independent factors for excellent cosmetic outcome were: volume of tissue resected (p = 0.0001), type of surgery (p = 0.0001), breast radiation dose (p = 0.005), race (p = 0.002), and age (p = 0.007). Conclusions: Satisfactory cosmesis was recorded in 81% of patients. Impaired cosmetic results are more likely with improper orientation of tylectomy and axillary incisions, larger volume of breast resection, radiation dose to the entire breast in excess of 50.0 Gy, and concurrent administration of chemotherapy. Careful selection of treatment procedures for specific patients/tumors and refinement in surgical/irradiation techniques will enhance the cosmetic results in breast conservation therapy

  8. The Use of Biologic Therapies in Uveitis.

    Science.gov (United States)

    Schwartzman, Sergio; Schwartzman, Monica

    2015-12-01

    Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective

  9. Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

    OpenAIRE

    Heathfield, Sarah; Parker, Ben; Zeef, Leo; Bruce, Ian; Alexander, Yvonne; Collins, Fraser; Stone, Michael; Wang, Edward; Williams, Anwen S.; Wright, Helen L.; Thomas, Huw B.; Moots, Robert J.; Edwards, Steven W.; Bullock, Craig; Chapman, Victoria

    2017-01-01

    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vas...

  10. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

    Science.gov (United States)

    D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

    2011-02-01

    The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

  11. [Survey of studies on time factor in acupoint sticking therapy for the bronchial asthma].

    Science.gov (United States)

    Huang, Dong-e; Guo, Jian-hong; Lin, Ying

    2010-02-01

    Based on the retrieval of literatures in recent fifteen years, the time factors in the acupoint sticking therapy for the bronchial asthma are analyzed and compared in terms of the stage classification of patients, timing selection of acupoint sticking therapy and medication application, and times of application. The acupoint sticking therapy is mostly practiced during remittent stage of bronchial asthma; the timing selection is mostly during the hottest period of summer, the timing selection in certain cases is the coldest period of winter or any day; the duration of medication application is not consistent; therefore, the effectiveness of these cases is different. It may be that the ef fectiveness is proportional to the times and courses of acupoint sticking therapy for the bronchial asthma. In the future, the scientific designs which involve time factor are needed to elucidate the importance of time factor in acupoint sticking therapy for the bronchial asthma.

  12. Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection

    Directory of Open Access Journals (Sweden)

    Nadia Belmellat

    2017-11-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α blockade is an effective treatment for rheumatoid arthritis (RA and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.

  13. Impact of biological therapy on body composition of patients with Chron's disease

    Directory of Open Access Journals (Sweden)

    Julianne Campos dos Santos

    Full Text Available Summary Introduction: Protein-energy malnutrition in Crohn's disease (CD has been reported in 20 to 92% of patients, and is associated with increased morbidity and mortality and higher costs for the health system. Anti-TNF drugs are a landmark in the clinical management, promoting prolonged remission in patients with CD. It is believed that the remission of this disease leads to nutritional recovery. The effect of biological therapy on body composition and nutritional status is unclear. Method: Prospective study of body assessment by bioelectrical impedance method in patients with moderate to severe CD undergoing treatment with infliximab. The main outcome was the body composition before and after 6 months of anti-TNF therapy. Results: There was a predominance of females (52% with a mean age of 42±12 years. Most patients were eutrophic at baseline and remained so. There was an increase in all parameters of body composition after anti-TNF treatment: BMI (22.9±3.2 versus 25±3.8; p=0.005, waist circumference (88.1±6.7 versus 93.9±7.7; p=0.002, lean mass index (17.5±2.2 versus 18.2±2.3; p=0.000 and fat mass index (5.5±2.3 versus 6.8±2.3; p=0.000. Phase angle remained unchanged (6.2 versus 6.8; p=0.94. Conclusion: After therapy with IFX, all components of body composition increased, except for phase angle. The substantial increase in fat mass index and waist circumference led to concern regarding cardiovascular risk and, thus, to the need for further studies.

  14. Male infertility: lifestyle factors and holistic, complementary, and alternative therapies

    Directory of Open Access Journals (Sweden)

    David F Yao

    2016-01-01

    Full Text Available While we may be comfortable with an allopathic approach to male infertility, we are also responsible for knowledge about lifestyle modifications and holistic, complementary, and alternative therapies that are used by many of our patients. This paper provides an evidence-based review separating fact from fiction for several of these therapies. There is sufficient literature to support weight reduction by diet and exercise, smoking cessation, and alcohol moderation. Supplements that have demonstrated positive effects on male fertility on small randomized controlled trial (RCT include aescin, coenzyme Q 10 , glutathione, Korean red ginseng, L-carnitine, nigella sativa, omega-3, selenium, a combination of zinc and folate, and the Menevit antioxidant. There is no support for the use of Vitamin C, Vitamin E, or saffron. The data for Chinese herbal medications, acupuncture, mind-body practice, scrotal cooling, and faith-based healing are sparse or inconclusive.

  15. Sources of information on lymphoma associated with anti-tumour necrosis factor agents: comparison of published case reports and cases reported to the French pharmacovigilance system.

    Science.gov (United States)

    Théophile, Hélène; Schaeverbeke, Thierry; Miremont-Salamé, Ghada; Abouelfath, Abdelilah; Kahn, Valentine; Haramburu, Françoise; Bégaud, Bernard

    2011-07-01

    Anti-tumour necrosis factor (TNF) agents, through their intense immunoregulatory effect, have been suspected to increase the risk of malignant lymphoma. However, the classical epidemiological approaches conducted over about the last 10 years have not totally succeeded in addressing the question of a causal or artifactual association. Therefore, the analysis of a substantial set of case reports, although usually considered as poorly generalizable to the general population, could be particularly informative. Two main sources of case reports in postmarketing settings are available; publications in medical journals and reports to pharmacovigilance systems. The aim of the study was to compare the characteristics of case reports from both these sources in order to understand whether they provided the same information for the investigation of the causal link between lymphoma and anti-TNF agents. All case reports of malignant lymphoma in patients treated with an anti-TNF agent published in MEDLINE and all reports to the French pharmacovigilance system up to 1 February 2010 were identified. Cases of malignant lymphoma identified in postmarketing surveillance from both sources were compared regarding the following variables: age, sex, anti-TNF agent involved, indication for use, type of lymphoma, prior or concomitant immunosuppressive drugs and time to onset of lymphoma. A total of 81 published case reports and 61 cases reported to the French pharmacovigilance system were compared. In published reports, patients were younger (p = 0.03) and more frequently receiving a first anti-TNF treatment (p = 0.03), particularly infliximab (p = 0.03). Conversely, in the pharmacovigilance system reports, a succession of different anti-TNFs (p = 0.03) and adalimumab (p French pharmacovigilance system differed markedly for all characteristics tested, except sex and the use of prior or concomitant immunosuppressive drugs. Published case reports favoured convincing arguments

  16. Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

    Science.gov (United States)

    Martin, Donel M; Gálvez, Verònica; Loo, Colleen K

    2015-06-19

    Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for

  17. Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

    Science.gov (United States)

    Gonczi, Lorant; Kurti, Zsuzsanna; Rutka, Mariann; Vegh, Zsuzsanna; Farkas, Klaudia; Lovasz, Barbara D; Golovics, Petra A; Gecse, Krisztina B; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

    2017-08-08

    Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

  18. Clinical factors affecting the outcome in postradioactive iodine (RAI) therapy patients - Philippine Heart Center experience

    International Nuclear Information System (INIS)

    Quinon, A.; Oabel, E.; Jimeno, C.

    2007-01-01

    Full text: Clinical factors such as patient's age, duration of the underlying autoimmune thyroid stimulus and anti-thyroid drug therapy may affect the outcome of patients who underwent RAI therapy. Objective: To evaluate the clinical factors affecting the outcome of RAI therapy. Methodology: Patients (n=41) with Graves' disease treated with anti-thyroid drugs were followed up after Radioactive Iodine therapy treatment. Thyroid scan, 2 and 24 hours radioactive iodine uptake were taken to compute for the therapy dose (120 uci) (computed thyroid weight in gms) (24-hour I 131 uptake). Patients were then divided into groups (Group 1= hypothyroid, Group 2= euthyroid, Group 3 hyperthyroid) based on their thyroid function results (FT3, FT4, TSH) after 2, 4, 6, 12 months post-therapy. Clinical and physiologic factors were then correlated with the outcome. Results: The population consisted of 41 patients (male=8, female=33) with an overall incidence of Group 1= 17%, Group 2= 54% and Group 3= 29% posttherapy. Factors such as age, with their means (Groups 134, 2= 39, 3=39 p= 0.42) and gland uptake (24-hour Groups 1= 53, 2= 61 358, p= 0.41) were not associated with the remission rate. Other factors that were related to the length of the disease such as duration of symptoms (Groups 121, 2=24, 3= 29 months p0.68), duration of medicine prior to RAI therapy (Group 1= 10, 2= 15, 3= 18 months p=0.306) and gland weight (Groups 1=40 2=42 3=46 grams p=0.78) tends to have a higher mean values in therapy failure patients. Conclusion: Clinical factors studied showed no significant differences among patients developing hypothyroid, euthyroid or hyperthyroid state. The data suggested that treatment failures in patients with Graves' disease could be improved by lessening the time interval between the diagnosis and radioactive iodine therapy. (author)

  19. Anti-TNF: Novel treatment in ocular sarcoidosis

    OpenAIRE

    Escudero Bodenlle, Laura; Olea Vallejo, José Luis; Pons Crespí, Mateu; Aragón Roca, Juan Antonio; Costa-Jordao, Cátia; Tarragó Pérez, Ramón

    2017-01-01

    Obejtivo: Se pretende demostrar la utilidad de la angiografía con fluoresceína y verde de indocianina en el diagnóstico y manejo de la sarcoidosis ocular, así como la utilidad de los fármacos biológicos en esta patología. Métodos: Para ello, se presenta un caso clínico de sarcoidosis sistémica y ocular tratada durante años con corticoides e inmunomoduladores, con mal control de la enfermedad. La principal afectación era la del segmento posterior del ojo, con numerosos signos en coroides y ret...

  20. Factors associated with developmental concern and intent to access therapy following discharge from the NICU.

    Science.gov (United States)

    Pineda, Roberta G; Castellano, Alison; Rogers, Cynthia; Neil, Jeffrey J; Inder, Terrie

    2013-01-01

    To determine factors associated with mothers' concern about infant development and intent to access therapy services following neonatal intensive care unit (NICU) discharge. Infant medical factors, magnetic resonance imaging results, neurobehavior at term, maternal factors, and maternal perceptions about developmental concern and intent to access therapy at NICU discharge were prospectively collected in 84 infants born premature (concern and intent to access therapy at NICU discharge. Decreased developmental concern was reported by mothers with more children (P = .007). Infant stress signs (P = .038), higher maternal education (P = .047), reading books (P = .030), and maternal depression (P = .018) were associated with increased developmental concern. More maternal education was associated with more intent to access services (P = .040). Maternal factors, rather than infant factors, had important associations with caregiver concern. In contrast, abnormal term neurobehavior and/or the presence of cerebral injury were not associated with caregiver concern about development.

  1. Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy

    Directory of Open Access Journals (Sweden)

    Mankgopo M. Kgatle

    2016-01-01

    Full Text Available Prostate cancer (PCa is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment.

  2. Risk factors for nutritional status determination and indications for preventive nutrition therapy in hospitalized gastroenterological patients

    Directory of Open Access Journals (Sweden)

    Roganović Branka

    2007-01-01

    Full Text Available Background/Aim. Risk factors for the intrahospital nutritional status worsening (NSW have not been precisely defined in the literature. The objective was defining thoese factors among gastroenterological patients and defining the risk patients requiring a preventive nutritional therapy. Methods. In 650 gastroenterological patients, NSW was evaluated on the basis of reducing of the six parameters: body weight, body mass index (BMI, triceps skinfold thickness (TSF, midupper arm muscle circumference (MAMC, serum albumin level (ALB, and lymphocyte count (LYM. The influence on NSW was tested for 13 factors concerning characteristics of the patient, disease, and diagnostic procedures. Among the factors influencing significantly the NSW, primary and secondary risk factors were selected. After scoring of risk factors had been performed, the risk-score for NSW (RSNSW was defined. The critical value of RSNSW which required preventive nutritional therapy was also calculated. Results. The incidence of NSW was in the range 29.2%−57.9%. The presence of general complications and severe disease activity were considered as primary risk factors, whereas malignant disease, age above 71, hepato-billiary tract involvement, hospitalization longer than 14 days, and mobility worsening were considered as secondary risk factors. The best predictive value for the NSW was proved for the RSNSW ≥ 6. Because of that, preventive nutritional therapy should be indicated in patients presenting with both primary risk factors or in patients presenting with one primary factor combined with three secondary risk factors at least. Conclusion. There are 7 risk factors for NSW in gastroenterological patients, but they are not of the same importance - two primary and five secondary risk factors can be differentiated. Preventive nutritional therapy is indicated only in patients having both primary risk factors or in those presenting with one primary risk factor combined with three

  3. Vedolizumab as a Treatment for Crohn’s Disease and Ulcerative Colitis

    OpenAIRE

    Ha, Christina; Kornbluth, Asher

    2014-01-01

    The management of Crohn’s disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lo...

  4. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  5. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

    Science.gov (United States)

    Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

    2017-03-28

    Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

  6. Analysis of the factors motivating HCV-infected patients to accept interferon therapy

    Directory of Open Access Journals (Sweden)

    Nagao Yumiko

    2012-08-01

    Full Text Available Abstract Background The aims of this study were to analyze factors motivating the acceptance of interferon (IFN therapy and to clarify the prevalence of oral mucosal diseases in hepatitis C virus (HCV-infected Japanese patients treated with IFN. Findings A total of 94 HCV-infected patients who were admitted to our hospital for IFN therapy were asked questions regarding their motivation to accept IFN therapy and were investigated for the presence of oral lichen planus (OLP before and during IFN treatment. Recommendation and encouragement from other people were the most common factors motivating the acceptance of IFN therapy (49/94, 52.13%. The other motivators were independent decision (30.85%, economic reasons (5.32%, and others. According to multivariate analysis, three factors – sex (male, retreatment after previous IFN therapy, and independent decision to accept IFN therapy - were associated with patients after curative treatment of hepatocellular carcinoma (HCC. The adjusted odds ratios for these three factors were 26.06, 14.17, and 8.72, respectively. The most common oral mucosal lesions included OLP in 11 cases (11.70%. One patient with OLP had postoperative squamous cell carcinoma of the tongue. The rate of sustained virological response (SVR was 45.45% in cases with OLP and 54.55% in cases without OLP. There were no patients who discontinued IFN therapy because of side effects such as oral mucosal diseases. Conclusions We should give full explanation and recommend a course of treatment for a patient to accept IFN therapy. The system to support liver disease as well as oral diseases is also necessary for patient treated for IFN therapy.

  7. Factors associated with the lack of antiretroviral therapy initiation ...

    African Journals Online (AJOL)

    that provide antenatal care (ANC) services also provide PMTCT services. ... This open-access article is distributed under. Creative ..... Karcher H, Omondi A, Odera J, Kunz A, Harms G. Risk factors for treatment denial and loss to follow-up in an ...

  8. Innovative physical therapy practice: a qualitative verification of factors that support diffusion of innovation in outpatient physical therapy practice.

    Science.gov (United States)

    Sabus, Carla; Spake, Ellen

    2016-01-01

    New ideas, methods, and technologies spread through cultures through typical patterns described by diffusion of innovation (DOI) theory. Professional cultures, including the physical therapy profession, have distinctive features and traditions that determine the adoption of practice innovation. The Consolidated Framework for Implementation Research (CFIR) proposes a framework of innovation implementation specific to health care services. While the CFIR has been applied to medical and nursing practice, it has not been extended to rehabilitation professions. The purpose of this qualitative study was to verify the CFIR factors in outpatient physical therapy practice. Through a nomination process of area rehabilitation managers and area directors of clinical education, 2 exemplar, outpatient, privately owned physical therapy clinics were identified as innovation practices. A total of 18 physical therapists (PTs), including 3 owners and a manager, participated in the study. The 2 clinics served as case studies within a qualitative approach of directed content analysis. Data were collected through observation, spontaneous, unstructured questioning, workflow analysis, structured focus group sessions, and artifact analysis including clinical documents. Focus group data were transcribed. All the data were analyzed and coded among 4 investigators. Through data analysis and alignment with literature in DOI theory in health care practice, the factors that determine innovation adoption were verified. The phenomena of implementation in PT practice are largely consistent with models of implementation in health care service. Within the outpatient practices studied, patient-centered care and collaborative learning were foundational elements to diffusion of an innovation. Innovation in outpatient physical therapy practice can be understood as a social process situated within the culture of the physical therapy professional that follows predictable patterns that strongly align with

  9. Exposure to occupational therapy as a factor influencing recruitment to the profession.

    Science.gov (United States)

    Byrne, Nicole

    2015-08-01

    This article provides insight into the impact that exposure to an occupational therapist, in personal capacity or via a professional interaction, has on the decision to enter an occupational therapy undergraduate programme. A quantitative survey was completed by 139 occupational therapy students. The survey tool focussed on the students' exposure to a range of allied health professions (e.g. occupational therapy, physiotherapy, psychology) and investigated how exposure to occupational therapy had influenced their decision to enter the programme. The results indicated that over 70% of respondents had personal professional exposure to occupational therapy prior to making a career decision. Exposure most frequently involved occupational therapy intervention of a friend or family member. The majority of students who had professional exposure to occupational therapy (e.g. family, self, friend received occupational therapy) identified that it was the most influential factor in their career choice. Forty per cent of the occupational therapy students did not enter the programme straight from school and the influence of 'working with an occupational therapist' was noteworthy for mature aged students. Occupational therapists need to consider that every interaction they have with the community provides valuable information regarding the profession and gives insight into occupational therapy as a potential career path for other people. Additionally, the current research identifies there were differences in the impact, type and number of exposures for different student groups, and this potentially offers some insight into ways in which occupational therapy could target specific groups within the community to increase future diversity in the profession. © 2015 Occupational Therapy Australia.

  10. Psychological factors addressed in cognitive behaviour therapy for paediatric functional abdominal pain: Which are most important to target?

    NARCIS (Netherlands)

    van der Veek, Shelley M. C.; de Haan, Else; Derkx, H. H. F.; Benninga, Marc A.; Boer, Frits

    2017-01-01

    The effectiveness of cognitive behaviour therapy for paediatric functional abdominal pain leaves room for improvement. We studied which factors addressed in cognitive behaviour therapy relate most strongly to the physical and psychological functioning of children with functional abdominal pain and

  11. How do patients with inflammatory bowel disease want their biological therapy administered?

    LENUS (Irish Health Repository)

    Allen, Patrick B

    2010-01-01

    BACKGROUND: Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn\\'s Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices. METHODS: An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose. RESULTS: One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: "I do not like the idea of self-injecting," (67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice

  12. Atelocollagen sponge and recombinant basic fibroblast growth factor combination therapy for resistant wounds with deep cavities.

    Science.gov (United States)

    Nakanishi, Asako; Hakamada, Arata; Isoda, Ken-ichi; Mizutani, Hitoshi

    2005-05-01

    Recent advances in bioengineering have introduced materials that enhance wound healing. Even with such new tools, some deep ulcers surrounded by avascular tissues, including bone, tendon, and fascia, are resistant to various therapies and easily form deep cavities with loss of subcutaneous tissue. Atelocollagen sponges have been used as an artificial dermis to cover full-thickness skin defects. Topical recombinant human basic fibroblast growth factor has been introduced as a growth factor to induce fibroblast proliferation in skin ulcers. We applied these materials in combination in two patients with deep resistant wounds: one with a cavity reaching the mediastinum through a divided sternum and one with deep necrotic wounds caused by electric burns. These wounds did not respond to the topical basic fibroblast growth factor alone. In contrast, the combination therapy closed the wounds rapidly without further surgical treatment. This combination therapy is a potent treatment for resistant wounds with deep cavities.

  13. Multiple Targets for Novel Therapy of FSGS Associated with Circulating Permeability Factor

    Directory of Open Access Journals (Sweden)

    Virginia J. Savin

    2017-01-01

    Full Text Available A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A or anti-immunoglobulin, or lipopheresis. Oral or intravenous galactose also decreases Palb activity. Studies of glomeruli have shown that several strategies prevent the action of FSGS sera. These include blocking receptor-ligand interactions, modulating cell reactions using indomethacin or eicosanoids 20-HETE or 8,9-EET, and enhancing cytoskeleton and protein interactions using calcineurin inhibitors, glucocorticoids, or rituximab. We have identified cardiotrophin-like cytokine factor 1 (CLCF-1 as a candidate for the permeability factor. Therapies specific to CLCF-1 include potential use of cytokine receptor-like factor (CRLF-1 and inhibition of Janus kinase 2. Combined therapy using multiple modalities offers therapy to reverse proteinuria and prevent scarring.

  14. Innovative physical therapy practice: a qualitative verification of factors that support diffusion of innovation in outpatient physical therapy practice

    Directory of Open Access Journals (Sweden)

    Sabus C

    2016-12-01

    Full Text Available Carla Sabus,1 Ellen Spake2 1Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS, 2Rockhurst University, Kansas City, MO, USA Background and purpose: New ideas, methods, and technologies spread through cultures through typical patterns described by diffusion of innovation (DOI theory. Professional cultures, including the physical therapy profession, have distinctive features and traditions that determine the adoption of practice innovation. The Consolidated Framework for Implementation Research (CFIR proposes a framework of innovation implementation specific to health care services. While the CFIR has been applied to medical and nursing practice, it has not been extended to rehabilitation professions. The purpose of this qualitative study was to verify the CFIR factors in outpatient physical therapy practice.Design: Through a nomination process of area rehabilitation managers and area directors of clinical education, 2 exemplar, outpatient, privately owned physical therapy clinics were identified as innovation practices. A total of 18 physical therapists (PTs, including 3 owners and a manager, participated in the study.Methods: The 2 clinics served as case studies within a qualitative approach of directed content analysis. Data were collected through observation, spontaneous, unstructured questioning, ­workflow analysis, structured focus group sessions, and artifact analysis including clinical documents. Focus group data were transcribed. All the data were analyzed and coded among 4 investigators.Results: Through data analysis and alignment with literature in DOI theory in health care practice, the factors that determine innovation adoption were verified. The phenomena of implementation in PT practice are largely consistent with models of implementation in health care service. Within the outpatient practices studied, patient-centered care and collaborative learning were foundational

  15. The Factor Structure of The Working Alliance Inventory in Cognitive-Behavioral Therapy

    Science.gov (United States)

    Andrusyna, Tomasz P.; Tang, Tony Z.; DeRubeis, Robert J.; Luborsky, Lester

    2001-01-01

    Studies of the therapeutic alliance in cognitive-behavioral therapy (CBT) have varied in their results, necessitating a deeper understanding of this construct. Through an exploratory factor analysis of the alliance in CBT, as measured by the Working Alliance Inventory (shortened, observer-rated version), the authors found a two-factor structure of alliance that challenges the commonly accepted one general factor of alliance. The results suggest that the relationship between therapist and client (Relationship) may be largely independent of the client's agreement with and confidence in the therapist and CBT (Agreement/ Confidence), necessitating independent measures of these two factors, not one measure of a general alliance factor. PMID:11402080

  16. Factors influencing the degree and pattern of parental involvement in play therapy for sexually abused children.

    Science.gov (United States)

    Hill, Andrew

    2009-01-01

    Although much has been written about the role of therapists in children's recovery from child sexual abuse, relatively little attention has been paid to the role of nonoffending parents. This study investigated the work of a team of therapists who sometimes included such parents in therapy sessions with children. The study sought to understand what factors were influencing the degree and pattern of parental involvement and to understand what effect these patterns of parental involvement were having on the process and outcomes of therapy. The study successfully identified a range of factors influencing the patterns of parental involvement, but more research will be needed to understand the effect on outcomes.

  17. Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

    Directory of Open Access Journals (Sweden)

    Mridula Krishnan

    2017-08-01

    Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

  18. Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia

    2008-12-01

    To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

  19. Predicting and influencing voice therapy adherence using social-cognitive factors and mobile video.

    Science.gov (United States)

    van Leer, Eva; Connor, Nadine P

    2015-05-01

    Patient adherence to voice therapy is an established challenge. The purpose of this study was (a) to examine whether adherence to treatment could be predicted from three social-cognitive factors measured at treatment onset: self-efficacy, goal commitment, and the therapeutic alliance, and (b) to test whether the provision of clinician, self-, and peer model mobile treatment videos on MP4 players would influence the same triad of social cognitive factors and the adherence behavior of patients. Forty adults with adducted hyperfunction with and without benign lesions were prospectively randomized to either 4 sessions of voice therapy enhanced by MP4 support or without MP4 support. Adherence between sessions was assessed through self-report. Social cognitive factors and voice outcomes were assessed at the beginning and end of therapy. Utility of MP4 support was assessed via interviews. Self-efficacy and the therapeutic alliance predicted a significant amount of adherence variance. MP4 support significantly increased generalization, self-efficacy for generalization, and the therapeutic alliance. An interaction effect demonstrated that MP4 support was particularly effective for patients who started therapy with poor self-efficacy for generalization. Adherence may be predicted and influenced via social-cognitive means. Mobile technology can extend therapy to extraclinical settings.

  20. 3D conformal radiation therapy and hormonal therapy for localized prostate cancer: Is age a limiting factor?

    International Nuclear Information System (INIS)

    Faure, A.; Negrea, T.; Lechevallier, E.; Coulange, C.; Murraciole, X.; Jouvea, E.; Sambuca, R.; Cowen, D.

    2011-01-01

    No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9 300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71 92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67 80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P ≡ ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients. (authors)

  1. Wound infections after median sternotomy treated by VAC therapy, summary of results, and risk factor analysis.

    Science.gov (United States)

    Hulman, M; Bezak, B; Artemiou, P; Cikrai, R

    2017-01-01

    The aim of this study is to summarize results and analyze risk factors for the development of wound infection in heart surgery patients after median sternotomy. In this retrospective analysis with assessment of multiple risk factors, we examined 143 patients with infection after median sternotomy treated with VAC therapy from total of 4,650 patients operated in our department from 2012 to 2015. Total of 143 patients developed significant SSI treated by VAC therapy following cardiac surgery. Of these, only 14 patients developed DSWI and one patient was diagnosed with suspected osteomyelitis. BMI, female gender, and use of BIMA proved to be statistically significant risk factors in our study (p infection (p infection proved to be a significant prognostic factor for patients' outcome (p infection (Tab. 3, Ref. 30).

  2. Patients' views toward knee osteoarthritis exercise therapy and factors influencing adherence - a survey in China.

    Science.gov (United States)

    Zhou, Zhiwei; Hou, Yunfei; Lin, Jianhao; Wang, Kai; Liu, Qiang

    2018-05-01

    To understand the views toward exercise therapy for knee osteoarthritis (KOA) in China and to analyze factors affecting treatment adherence. A survey-based study, which included multiple choice and open-ended questions on knee OA exercise therapy was conducted in a Chinese population. The content included the respondents' attitudes and beliefs, willingness to receive treatment, and reasons why they could or could not adhere to the treatment. We used Chi-squared tests to compare cognitive differences between the patients and non-patient groups. A total of 1,069 people responded to the questionnaire, and the response rate was 81.8%. A total of 93.6% of the patients thought that they could adhere to the exercise treatment if they received professional advice and prescriptions. The following questionnaire items achieved consensus: 'Increasing the strength of the muscles around the knee stops the knee pain from getting worse,' 'It is the person's own responsibility to continue doing their exercise program,' 'How helpful the exercise program will be determines how well a person sticks to it,' 'Health professionals should educate patients with knee pain about how to change their lifestyle for the better,' and 'Exercise for knee pain is most helpful when it is designed for each person, to suit their own particular needs.' Patient adherence was affected by multiple factors, and some negative factors included 'forgetfulness,' 'getting joint symptoms improved after therapy,' 'professional guidance, subsequent monitoring and supervision,' 'willing to enhance overall health and quality of life,' 'having no time,' 'occupational factors,' 'considering that the pain would worsen while/after exercise,' and 'family factors.' A general Chinese population accepted exercise therapy for treating KOA in our survey. Education is necessary because patients were uncertain and had misunderstandings regarding the potential benefits of exercise therapy. Some factors related to treatment

  3. Reduction of Risk Factors in Patients with Behavioral Dysphonia After Vocal Group Therapy.

    Science.gov (United States)

    Silva, Wégina Jordâna Nascimento da; Lopes, Leonardo Wanderley; Macedo, Anny Elizabety Ramalho de; Costa, Denise Batista da; Almeida, Anna Alice Figueiredo de

    2017-01-01

    The origin and development of dysphonia, particularly behavioral dysphonia, is associated with several risk factors. Here, we verified the effectiveness of group therapy in reducing the risk factors, and established the association between risk factors and sex, age, profession, and diagnosis of laryngeal disorders in patients with behavioral dysphonia. This is a descriptive, quantitative, field intervention study. Participants (n = 26, adult patients of both sexes), with a diagnosis of behavioral dysphonia, received group therapy intervention. Data for risk factors were collected pre- and posttherapy using the Vocal Screening Protocol. The data were analyzed using descriptive and inferential statistics (Student t test, chi-squared test or Spearman correlation test). The majority (80.8%, n = 21) of patients were female, 65.4% (n = 17) were not in a vocal profession, and 42.3% (n = 11) presented with a lesion in the membranous portion of the vocal fold. The number of personal risk factors decreased after group therapy (P = 0.04). In addition, age was correlated with total (P = 0.001), environmental (P = 0.002), and personal (P = 0.003) vocal risk factors posttherapy. This study revealed an association between the reduction of personal risk factors and vocal group therapy, and a correlation between age and total, environmental, and personal vocal risk factors posttherapy. Thus, maintenance and origins of the behaviors that modify the behavioral aspects of the participants directly influence the production of individual vocal habits. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  4. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    Directory of Open Access Journals (Sweden)

    Gustavo Romero‐Velez, MD

    2014-04-01

    Conclusions: ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero‐Velez G, Lisker‐Cervantes A, Villeda‐Sandoval CI, Sotomayor de Zavaleta M, Olvera‐Posada D, Sierra‐Madero JG, Arreguin‐Camacho LO, and Castillejos‐Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30.

  5. Stevens-Johnson syndrome in a patient with rheumatoid arthritis during long-term etanercept therapy.

    Science.gov (United States)

    Owczarczyk-Saczonek, Agnieszka; Zdanowska, Natalia; Znajewska-Pander, Aleksandra; Placek, Waldemar

    2016-03-31

    Etanercept and other anti-TNF-alpha agents have been indicated as a therapeutic option in severe drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Etanercept has been shown to quickly reduce the detachment of the epidermis and shorten healing time. Cases of etanercept-induced severe adverse drug reactions were also described. A 27-year-old woman with a 4-year history of etanercept and sulfasalazine treatment for rheumatoid arthritis was admitted with Stevens-Johnson syndrome. The patient received one dose of an OTC drug containing acetaminophen, phenylephrine and pheniramine two days prior to developing fist mucocutaneous symptoms. The most probable causative agent was paracetamol. Throughout the successful routine therapy of Stevens-Johnson syndrome etanercept therapy was continued. Sulfosalazin administration was stopped and administered again after recovery with no recurrence of the skin and mucosal symptoms. This case indicates that there is no justification for discontinuation of long-term anti-TNF-alpha treatment in patients who develop Stevens- Johnson syndrome / toxic epidermal necrolysis.

  6. Gene therapy with growth factors for periodontal tissue engineering–A review

    Science.gov (United States)

    Gupta, Shipra; Mahendra, Aneet

    2012-01-01

    The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

  7. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  8. Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Wyss, Natascha; Zwahlen, Marcel; Bohlius, Julia

    2016-01-01

    BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...

  9. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

    NARCIS (Netherlands)

    Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K.; van Wijk, Albert C.; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C.; van Gulik, Thomas M.; Storm, Gert; Heger, Michal

    2016-01-01

    Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of

  10. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

    NARCIS (Netherlands)

    Weijer, R.; Broekgaarden, M.; Krekorian, M.; Alles, L.K.; van Wijk, A.C; Mackaaij, C.; Verheij, J.; van der Wal, A.C.; van Gullik, T.M.; Storm, Gerrit; Heger, M.

    2016-01-01

    Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression

  11. Voices of Family Therapy Doctoral Students of Color: Aspirations and Factors Influencing Careers in Academia

    Science.gov (United States)

    Miller, John K.; Stone, Dana J.

    2011-01-01

    The authors examined factors influencing career aspirations of doctoral students of color in family therapy doctoral programs across the country, with a special focus on careers in the professoriate. Qualitative interviews were conducted with students at varying levels of degree completion. Respondents discussed barriers to careers in academia as…

  12. Factors affecting the stability of visual function following cessation of occlusion therapy for amblyopia.

    Science.gov (United States)

    Tacagni, Daniel J; Stewart, Catherine E; Moseley, Merrick J; Fielder, Alistair R

    2007-06-01

    To identify factors that predict which children with amblyopia are at greatest risk of regression of visual acuity (VA) following the cessation of occlusion therapy. A retrospective analysis was performed of 182 children (mean age at cessation of treatment; 5.9+/-1.6 years) who had undergone occlusion therapy for unilateral amblyopia, and had been followed up at least once within 15 months of cessation. Statistical analysis was used to identify whether change in VA following treatment cessation had any association with various factors, including the child's age, type of amblyopia, degree of anisometropia, initial severity of amblyopia, binocular vision status, length and dose of occlusion therapy, and VA response to treatment. At 1 year, follow-up from treatment cessation, children with "mixed" amblyopia (both anisometropia and strabismus) demonstrated significantly (p=0.03) greater deterioration in VA (0.11+/-0.11 log units) than children with only anisometropia (0.02+/-0.08 log units) or only strabismus (0.05+/-0.10 log units). However, none of the other factors investigated were found to be significant predictors. This study supports previous research that it is possible to identify those children most at risk of deterioration in VA following cessation of occlusion therapy. The presence of mixed amblyopia was the only risk factor identified in this study. Management of amblyopia should take this into account, with a more intensive follow-up recommended for those with both anisometropia and strabismus (mixed) amblyopia.

  13. Interleukin-1beta and TNF-alpha: reliable targets for protective therapies in Parkinson´s Disease?

    Directory of Open Access Journals (Sweden)

    María Celeste Leal

    2013-04-01

    Full Text Available Neuroinflammation has received increased attention as a target for putative neuroprotective therapies in Parkinson´s Disease (PD. Two prototypic pro-inflammatory cytokines Interleukin-1beta (IL-1 and Tumor necrosis factor-alpha (TNF have been implicated as main effectors of the functional consequences of neuroinflammation on neurodegeneration in PD models. In this review, we describe that the functional interaction between these cytokines in the brain differs from the periphery (e.g. their expression is not induced by each other and present data showing predominantly a toxic effect of these cytokines when expressed at high doses and for a sustained period of time in the substantia nigra pars compacta (SN. In addition, we highlight opposite evidence showing protective effects of these two main cytokines when conditions of duration, amount of expression or state of activation of the target or neighboring cells are changed. Furthermore, we discuss these results in the frame of previous disappointing results from anti-TNF clinical trials against Multiple Sclerosis, another neurodegenerative disease with a clear neuroinflammatory component. In conclusion, we hypothesize that the available evidence suggests that the duration and dose of IL-1 or TNF expression is crucial to predict their functional effect on the SN. Since these parameters are not amenable for measurement in the SN of PD patients, we call for an in-depth analysis to identify downstream mediators that could be common to the toxic (and not the protective effects of these cytokines in the SN. This strategy could spare the possible neuroprotective effect of these cytokines operative in the patient at the time of treatment, increasing the probability of efficacy in a clinical setting. Alternatively, receptor-specific agonists or antagonists could also provide a way to circumvent undesired effects of general anti-inflammatory or specific anti IL-1 or TNF therapies against PD.

  14. Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

    Science.gov (United States)

    Sadashiv, Mucheli Shravan; Rupali, Priscilla; Manesh, Abi; Kannangai, Rajesh; Abraham, Ooriapadickal Cherian; Pulimood, Susanne A; Karthik, Rajiv; Rajkumar, S; Thomas, Kurien

    2017-12-01

    Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Univariate analysis showed significant association with 1) Self-reported nonadherenceART and thus help development of targeted interventions.

  15. Radiation therapy for Kasabach-Merritt syndrome. Analysis of unfavorable factors in 5 children

    International Nuclear Information System (INIS)

    Kawamori, Jiro; Saito, Tsutomu; Tanaka, Yoshiaki; Sato, Katsuhiko.

    1996-01-01

    During the past 10 years, five infants with Kasabach-Merritt syndrome (K-M) receiving radiation therapy were reported. We investigated whether radiation therapy for K-M was useful and what the unfavorable factors of K-M were. During the past 10 years, we have treated five infants with K-M. The syndrome occurred at ages ranging from birth to 4 months. The incidence of female to male ratio was 3:2. Among 5 cases, the site of hemangioma was as follows; shoulder, anterior chest wall, lower abdominal wall, face and neck and inguinal site. All 5 cases received medication to control the coagulopathy including prednisone and blood transfusion at first. Because the platelet count and the bleeding tendency did not improve in any case, these cases received radiation therapy. Total dose ranged from 5 to 10 Gy and fraction-size ranged from 0.5 to 1.75 Gy. Irradiation session was 2 or 3 times per week. In 5 cases, 4 cases showed cure of bleeding tendency and disappearance of tumor, and survived. In these 4 cases, normalization of platelet count was obtained at the early phase of dose ranging from 3 to 5 Gy by radiation therapy. In the remaining case, bleeding tendency was improved at the late phase by initial radiation therapy, however, after that immediately relapsed. In this case, the salvage radiation therapy was not effective and she died from airway obstruction. This case was of neonatal age and had bulky neck tumor. We recognized that radiation therapy was effective for K-M. A serious case was of neonatal age and had bulky neck tumor. It was estimated that the unfavorable factors of K-M were neonatal case and bulky neck tumor case. (author)

  16. Occupational Therapy Practitioners with Occupational Musculoskeletal Injuries: Prevalence and Risk Factors.

    Science.gov (United States)

    Alnaser, Musaed Z

    2015-12-01

    The purpose of this study was to examine the prevalence and risk factors of occupational musculoskeletal injuries (OMIs) among occupational therapy practitioners over a 12-month period. A self-administered questionnaire mailed to 500 randomly selected practicing occupational therapists (OTs) and occupational therapy assistants (OTAs) living in the state of Texas. A response rate of 38 % was attained with 192 questionnaires returned. In a 12-months working period, 23 % of occupational therapy practitioners experienced musculoskeletal injuries. Muscle strain (52 %) was most reported injury and lower back (32 %) was most injured body part. Years of practicing experience (t = 2.83, p = 0.01), and age x(2)(2, N = 192) = 8.28, p = 0.02 were found as significant factors associated with injuries among OTAs. No factors were significantly associated with injuries among OTs. Patient handling was the primary factor associated with injuries. Also, minimal experience and older age were concluded as risk factors that might contribute to OMIs.

  17. In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

    Science.gov (United States)

    Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

    1993-10-01

    The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

  18. Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway.

    LENUS (Irish Health Repository)

    Korpanty, Grzegorz

    2010-01-01

    Lung cancer (LC) is a leading cause of death worldwide. Recent advances in chemotherapeutic agents have not yielded any significant improvement in the prognosis of patients with LC. The five-year survival rate for all combined disease stages remains about 15%. For this reason, new therapies such as those that inhibit tumor angiogenesis or block activity of growth factor receptors are of special interest in this group of patients. In this review we will summarize the most recent clinical data on biologic therapies that inhibit tumor angiogenesis in LC, focusing on those that are most clinically relevant.

  19. Risk Factors for Pelvic Insufficiency Fractures in Locally Advanced Cervical Cancer Following Intensity Modulated Radiation Therapy

    DEFF Research Database (Denmark)

    Ramlov, Anne; Pedersen, Erik Morre; Røhl, Lisbeth

    2017-01-01

    and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition......PURPOSE: To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin...

  20. Smoking does influence disease behaviour and impacts the need for therapy in Crohn's disease in the biologic era.

    Science.gov (United States)

    Nunes, T; Etchevers, M J; Domènech, E; García-Sánchez, V; Ber, Y; Peñalva, M; Merino, O; Nos, P; Garcia-Planella, E; Casbas, A G; Esteve, M; Taxonera Samsó, C; Montoro Huguet, M; Gisbert, J P; Martín Arranz, M D; García-Sepulcre, M F; Barreiro-de Acosta, M; Beltrán, B; Alcaide Suárez, N; Saro Gismera, C; Cabriada, J L; Cañas-Ventura, A; Gomollón, F; Panés, J

    2013-10-01

    Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers. © 2013 John Wiley & Sons Ltd.

  1. Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Ainsworth, Mark; Steenholdt, Casper

    2009-01-01

    (s) for these response failures are not clear but inter-individual and even intra-individual differences in bioavailability and pharmacokinetics may contribute. Furthermore, immunogenicity of the drugs, causing patients to develop anti-drug antibodies (ADAs), contributes to treatment failure. Monitoring patients...... for circulating levels of functional anti-TNF drugs and ADAs is therefore warranted so that treatment can be tailored to the individual patient (individual medicine or personal medicine) in order that effective and economical long-term therapy can be given with minimal risks to the patients....

  2. The use of human factors methods to identify and mitigate safety issues in radiation therapy

    International Nuclear Information System (INIS)

    Chan, Alvita J.; Islam, Mohammad K.; Rosewall, Tara; Jaffray, David A.; Easty, Anthony C.; Cafazzo, Joseph A.

    2010-01-01

    Background and purpose: New radiation therapy technologies can enhance the quality of treatment and reduce error. However, the treatment process has become more complex, and radiation dose is not always delivered as intended. Using human factors methods, a radiotherapy treatment delivery process was evaluated, and a redesign was undertaken to determine the effect on system safety. Material and methods: An ethnographic field study and workflow analysis was conducted to identify human factors issues of the treatment delivery process. To address specific issues, components of the user interface were redesigned through a user-centered approach. Sixteen radiation therapy students were then used to experimentally evaluate the redesigned system through a usability test to determine the effectiveness in mitigating use errors. Results: According to findings from the usability test, the redesigned system successfully reduced the error rates of two common errors (p < .04 and p < .01). It also improved the mean task completion time by 5.5% (p < .02) and achieved a higher level of user satisfaction. Conclusions: These findings demonstrated the importance and benefits of applying human factors methods in the design of radiation therapy systems. Many other opportunities still exist to improve patient safety in this area using human factors methods.

  3. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  4. Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Szlachcic A

    2016-08-01

    Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

  5. Factors influencing visual rehabilitation after occlusion therapy in unilateral amblyopia in children.

    Science.gov (United States)

    Menon, Vimla; Chaudhuri, Zia; Saxena, Rohit; Gill, Kulwant; Sachdeva, M M

    2005-12-01

    Amblyopia is one of the most common causes of visual impairment in adults and children, and visual loss may be permanent if not treated in time. Though many studies have been done on occlusion therapy which is the mainstay in the treatment of unilateral amblyopia, discrepancies exist in literature about quantification of treatment and follow up measures. The present study was undertaken to evaluate the factors responsible for the successful outcome of treatment and the optimum time required for the same in children with unilateral amblyopia. Baseline characteristics of 63 verbal patients with unilateral amblyopia (strabismic, anisometropic, mixed) referred to the Strabismus and Amblyopia Clinic at the Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi between September 2001 to December 2002 who improved to the desired level of visual acuity after treatment for amblyopia in the mentioned time period, were analyzed to assess for factors that directly or indirectly influenced the optimum visual rehabilitation and the average duration of therapy required for the same. The evaluation included assessment of the baseline best-corrected visual acuity (BCVA) and refractive status in both eyes, the age at presentation, the type of amblyopia present, fixation pattern in the amblyopic eye, inter-eye visual acuity difference, and evaluation of compliance through a parental diary system. Baseline BCVA in the amblyopic eye was similar in all the three groups. Patients with anisometropic amblyopia showed a quicker response to therapy. Compliance to treatment was the major factor affecting the overall time required for a successful outcome in most cases. The overall time required for the treatment to be successful (including the period of maintenance) was about 1,089 h. This hospital-based study showed that the average duration of occlusion therapy to achieve stable isoacuity was 7.2 months with an average occlusion of 6-7 h/day. Compliance to therapy was the most

  6. Risk factors for persistent atrial fibrillation following successful hyperthyroidism treatment with radioiodine therapy.

    Science.gov (United States)

    Zhou, Zhen-Hu; Ma, Long-Le; Wang, Le-Xin

    2011-01-01

    To investigate the predicting factors for persistent atrial fibrillation (AF) following radioiodine therapy for hyperthyroidism. Standard 12-lead ECG and 24-h Holter monitoring were performed in 94 patients (38 males, mean age 46.1±8.2 years) with persistent AF following radioiodine therapy for hyperthyroidism. Left ventricular (LV) function was assessed with two-dimensional echocardiography. Euthyroidism or hypothyroidism was achieved in 81% and 19% of the patients, respectively, after radioiodine therapy. At the end of follow-up (1.6±1.3 years), LV ejection fraction in the 52 patients with LV dysfunction was increased from 39.3±3.3% to 59.0±5.5% (ptreatment paroxysmal AF, no AF was documented during the follow-up. In the 45 patients with pre-treatment persistent AF, AF was found in 27 (60%) during the follow-up. Multivariate logistic regression analysis showed that more than 55 years old in age (RR 2.76, 95% CI: 1.16-8.79, phyperthyroidism (RR 3.08, 95% CI: 1.22-11.41, ptreatment atrial fibrillation (RR 2.96, 95% CI: 1.31-7.68, phyperthyroidism and pre-treatment duration of AF are risk factors for persistent AF following radioiodine therapy.

  7. Bleeding and asymptomatic overdose in patients under Vitamin K antagonist therapy: Frequency and risk factors

    Directory of Open Access Journals (Sweden)

    F. Ben Mbarka

    2018-03-01

    Full Text Available Background: Vitamin K antagonists are widely used in the treatment and prevention of thromboembolic disease. However, these drugs can cause serious side effects, especially bleeding. This study aims to evaluate frequency and risk factors of both bleeding and asymptomatic overdose in North African patients undergoing Vitamin K antagonist therapy. Methods: We performed a cross-sectional study in patients undergoing Vitamin K antagonist therapy. A statistical analysis has been conducted to identify overdose and bleeding risk factors by using chi-square test (p < .05. Results: One hundred and eleven patients were included. We recorded 14 cases of bleeding and 26 cases of asymptomatic overdose. Advanced age, poor adherence, concomitant use of paracetamol and history of previous bleeding are significant risk factors of over-anticoagulation. An INR value over 6 at admission, a high therapeutic target range for INR, concomitant use of acetylsalicylic acid, lack of information on overdose signs and measures to be taken in case of bleeding were identified as risk factors for bleeding. Conclusion: Most of the risk factors identified in our study seem to be related to patients lack of information and education. These results highlight the importance of creating a therapeutic patient education program. Keywords: Vitamin K antagonist, Bleeding, Risk factor, Overdose

  8. Trophic factors as modulators of motor neuron physiology and survival: implications for ALS therapy

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2014-02-01

    Full Text Available Motor neuron physiology and development depend on a continuous and tightly regulated trophic support from a variety of cellular sources. Trophic factors guide the generation and positioning of motor neurons during every stage of the developmental process. As well, they are involved in axon guidance and synapse formation. Even in the adult spinal cord an uninterrupted trophic input is required to maintain neuronal functioning and protection from noxious stimuli. Among the trophic factors that have been demonstrated to participate in motor neuron physiology are vascular endothelial growth factor (VEGF, glial-derived neurotrophic factor (GDNF, ciliary neurotrophic factor (CNTF and insulin-like growth factor 1 (IGF-1. Upon binding to membrane receptors expressed in motor neurons or neighboring glia, these trophic factors activate intracellular signaling pathways that promote cell survival and have protective action on motor neurons, in both in vivo and in vitro models of neuronal degeneration. For these reasons these factors have been considered a promising therapeutic method for amyotrophic lateral sclerosis (ALS and other neurodegenerative diseases, although their efficacy in human clinical trials have not yet shown the expected protection. In this review we summarize experimental data on the role of these trophic factors in motor neuron function and survival, as well as their mechanisms of action. We also briefly discuss the potential therapeutic use of the trophic factors and why these therapies may have not been yet successful in the clinical use.

  9. Impact of identifying factors which trigger bothersome tinnitus on the treatment outcome in tinnitus retraining therapy.

    Science.gov (United States)

    Molini, Egisto; Faralli, Mario; Calzolaro, Lucia; Ricci, Giampietro

    2014-01-01

    The aim of this work was to ascertain any differences in the effectiveness of rehabilitation therapy in relation to the presence or absence of a known negative reinforcement responsible for the tinnitus-related pathology. Between 1 January 2001 and 31 December 2008, we recruited 294 subjects suffering from incapacitating tinnitus and/or hyperacusis. The patients underwent tinnitus retraining therapy (TRT) according to the methods described by Jastreboff and Hazell [Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge, Cambridge University Press, 2004, pp 121-133]. We clinically assessed the presence or absence of known phenomena of associative learning, regarding the presence of adverse events temporally correlated with tinnitus and the treatment outcome. The separate analysis of the 2 subgroups shows a statistically significant difference in the improvement rate between the group with a known triggering factor and the group without a triggering factor, with a preponderance of the former with a 91% improvement rate versus approximately 56% for the latter. In our study, the inability to identify factors triggering bothersome tinnitus negatively affected the treatment outcome in TRT. © 2014 S. Karger AG, Basel.

  10. Associations between alcohol use, other psychosocial factors, structural factors and antiretroviral therapy (ART) adherence among South African ART recipients.

    Science.gov (United States)

    Morojele, Neo K; Kekwaletswe, Connie T; Nkosi, Sebenzile

    2014-03-01

    We examined whether alcohol use is associated with antiretroviral therapy (ART) adherence independently of structural and psychosocial factors among 304 male and female ART recipients in ART sites in Tshwane, South Africa. ART adherence was assessed by the CASE Adherence Index. Independent variables were demographic, structural, psycho-social, and alcohol use (AUDIT score) factors. In hierarchical multiple regression, demographic variables (Step 1) explained 4 % of variance in ART adherence (p ≤ 0.01). Variance explained increased to 16 % (p ≤ 0.001) after entering structural variables (Step 2); 19 % (p ≤ 0.001) after entering psychosocial variables (Step 3); and 24 % (p ≤ 0.001) after entering AUDIT score (Step 4). Alcohol use is independently associated with ART adherence.

  11. The Results and Prognostic Factors of Postoperative Radiation Therapy in the Early Stages of Endometrial Cancer

    International Nuclear Information System (INIS)

    Lee, Kyung Ja

    2008-01-01

    To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial

  12. Recurrent spleen enlargement during cyclic granulocyte-macrophage colony-stimulating factor therapy for myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Delmer, A.; Karmochkine, M.; Cadiou, M.; Gerhartz, H.; Zittoun, R.

    1990-01-01

    A 65-year-old woman with refractory anemia with excess of blasts received sequential courses of granulocyte-macrophage colony-stimulating factor therapy (GM-CSF) and low-dose cytosine arabinoside. Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111-indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen

  13. The discriminatory analysis about factors correlative with the early hypothyroidism after 131I therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Xiong Lingjing; Liang Changhua; Deng Haoyu; Li Xinhui; Hu Shuo

    2002-01-01

    Objective: To explore the factors correlative with the early hypothyroidism after 131 I therapy for Graves' hyperthyroidism so as to cure it and decrease the early hypothyroidism occurring and prevent it from becoming irreversible hypothyroidism. Methods: Logistic regression discriminatory analysis by introducing multiple factors from group data and forward stepwise selection of 11 independent variables of 240 hyperthyroidism patients from clinical data and 1 dependent variable from follow-up data after 131 I therapy was conducted. Univariate analysis of each observed factor was performed, too. Results: (1)The results of multivariate analysis showed that the age of patients, the weight of thyroid, the suffering situation, the curve of 131 I absorption rate and the giving 131 I dosage/g thyroid tissue were correlated to early hypothyroidism. The results of univariate analysis showed that the weight of thyroid, the highest absorption of 131 I, the total treatment dosage of 131 I were correlated to early hypothyroidism. (2) The logistic regression equation was statistically significant. (3) The positive and negative predicting accuracy of the early hypothyroidism occurring was 64.08 %, 78.83 %, respectively, the overall predicting accuracy was 72.50%. Conclusions: The dosage of 131 I for treatment of hyperthyroid is the key factor according to the five correlative factors which are relating to the early hypothyroidism and the discriminatory classification. Enhanced follow-up and in time supplement of thyroid hormone are important measures for preventing the early hypothyroidism from becoming irreversible hypothyroidism

  14. Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

    Directory of Open Access Journals (Sweden)

    I. S. Коlova

    2017-01-01

    Full Text Available Objective: To study the factors that influence the destination of suppressive antiviral therapy in patients with recurrent genital herpes doctors of different specialties.Material and Methods: The study was conducted based on an anonymous survey of professionals providing medical care to patients with genital herpes. The survey involved 67 experts – 44 dermatologist, 13 obstetricians and 10 urologists working in Skin and Venereal Diseases, Women’s consuitation post and Saint Petersburg clinics.Results: Most respondents indicated that among patients with genital herpes, seeking an appointment, dominated by patients with relapsing nature of the disease. Suppressive antiviral therapy is recommended 68,7% of specialists, including dermatologists 61,3%, 84,6% of obstetricians and gynecologists, and 80% of urologists. The main indications for its experts consider high frequency of relapses, the patient’s tendency to promiscuity, the desire of the patient with fewer relapses, and the emotional response of the patient for the presence of the disease. Do not prescribe suppressive therapy for recurrent genital herpes 31,4% of the doctors surveyed. Among the reasons for which are not appointed by the type of treatment, the patient is dominated by the rejection of this type of treatment, the lack of experience of the destination suppressive therapy, as well as the uncertainty of specialists in its effectiveness.Conclusion: Suppressive antiviral therapy is recommended 68,7% of specialists. Do not prescribe this type of treatment for recurrent genital herpes 31,4% of the doctors surveyed. The proportion of professionals who refuse the appointment of suppressive antiviral therapy, the highest among dermatologists (38,7% compared with 15,4% among obstetricians and 20% of urologists. The most frequent grounds for refusal from this type of treatment is the lack of confidence in its effectiveness. 

  15. Therapies based on inhibitors of the epidermal growth factor receptor: enclosing the future

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Lage, Agustin

    2007-01-01

    The Epidermal Growth Factor Receptor (EGFR) is considered an important target for rational drug design due to its key role in numerous tumors. Potential contribution of EGFR-related signaling pathways to promote tumorigenic processes, including cell proliferation, angiogenesis, and resistance to apoptosis has been well established. Two classes of anti-EGFR agents in late-stage clinical testing include monoclonal antibodies against extracellular EGFR domain (Cetuximab, Nimotuzumab) and small molecules tyrosine kinase inhibitors, which inhibit the receptor enzyme activity (Gefitinib, Erlotinib). A considerable body of evidence has emerged since its introduction in the treatment of cancer patients. However, important questions such as reliable surrogate markers to predict response to the treatment, or optimal sequence and combination of these agents with conventional therapies remain to be addressed. Identify and validate predictive factors to select patients likely to respond to EGFR inhibitors, such as mutations that confer resistance versus those associated with sensitivity is required. A better understanding of molecular mechanisms associated with antitumor activity will useful to predict the interaction of these agents with other therapies in order to avoid antagonisms or overlapping effects resulting in no adding effects. Finally, the benefits derived from EGFR inhibitors as first-line therapy in selected populations, and the optimal doses and ways to delivery to the tumor site resulting in optimal target modulation should be established by the ongoing investigation. (Author)

  16. Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

    Science.gov (United States)

    Kawara, Fumiaki; Fujita, Tsuyoshi; Morita, Yoshinori; Uda, Atsushi; Masuda, Atsuhiro; Saito, Masaya; Ooi, Makoto; Ishida, Tsukasa; Kondo, Yasuyuki; Yoshida, Shiei; Okuno, Tatsuya; Yano, Yoshihiko; Yoshida, Masaru; Kutsumi, Hiromu; Hayakumo, Takanobu; Yamashita, Kazuhiko; Hirano, Takeshi; Hirai, Midori; Azuma, Takeshi

    2017-03-21

    To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

  17. Factors influencing the use of outcome measures in physical therapy practice.

    Science.gov (United States)

    Wedge, Frances M; Braswell-Christy, Jennifer; Brown, Cynthia J; Foley, Kathleen T; Graham, Cecilia; Shaw, Sharon

    2012-02-01

    Use of outcome measures in physical therapy practice is central to evaluating the effectiveness of treatment interventions, providing accountability and addressing quality of physical therapy programs. There is limited discussion on barriers and facilitators to using outcome measures in physical therapy practice. The purpose of this study was to identify factors that influence a physical therapist when deciding to use outcome measures in clinical practice. Participants were 21 physical therapists, seven each from skilled nursing facilities, outpatient clinics, and inpatient rehabilitation facilities. A grounded theory approach was used for interview and data collection. Common themes were determined from the data and a theory developed to explain the rationale behind physical therapists' decisions to use or not use outcome measures in clinical practice. Three overlapping themes related to (1) concepts of time, (2) knowledge, and (3) facility culture were indentified as factors influencing the use of outcome measures. A fourth encompassing theme, professionalism, identified the value placed on the use of outcome measures in practice. Data revealed that therapists require more information on the outcome measures available, and this information needs to be easily accessible within the workplace. Therapists value information generated by using outcome measures in the clinical setting, but need information on what measures are available and psychometric properties. Information must be easily accessible and measures easy to use. Newer graduates and recent learners have a foundation in the use of outcome measures, but more needs to be done in the clinic and through continuing education to promote increased use and understanding.

  18. Risk factors associated with atherogenic dyslipidemia in the presence of optimal statin therapy.

    Science.gov (United States)

    Zhao, Wang; Zheng, Xi-Long; Jiang, Ze-Nan; Liao, Xiao-Bo; Zhao, Shui-Ping

    2017-12-01

    This study investigated the prevalence of atherogenic dyslipidemia (AD) in Chinese outpatients whose low-density lipoprotein cholesterol (LDL-C) levels reached the goals with statin monotherapy and evaluated the characteristics of these patients. An analysis of the Dyslipidemia International Survey-China study that was carried out at 122 hospitals in China. Among patients reaching their LDL-C goals, the presence of AD was defined as triglyceride levels ≥1.7mmol/L and/or low levels of high-density lipoprotein cholesterol (men: dyslipidemia, 13,551 patients reached LDL-C goals, and 7719 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, coronary heart disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. The intensity of statin therapy did not affect the prevalence of AD. There was a high prevalence of AD in Chinese patients with optimal statin treatment. Some risk factors associated with AD were identified, but these factors were slightly different according to two criteria/guidelines. The intensity of statin therapy did not reduce the prevalence of AD. A combination lipid therapy may be more suitable for Chinese patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Role of tumor necrosis factor in macrophage leishmanicidal activity in vitro and resistance to cutaneous leishmaniasis in vivo.

    Science.gov (United States)

    Theodos, C M; Povinelli, L; Molina, R; Sherry, B; Titus, R G

    1991-01-01

    Recombinant human tumor necrosis factor (TNF) and purified murine TNF were both able to activate macrophages to destroy intracellular Leishmania major in vitro. In addition, parasitizing macrophages with L. major markedly increased the ability of the cells to produce TNF. Finally, when mice were vaccinated with an avirulent form of L. major, the animals produced large amounts of TNF but no gamma interferon in response to infection with virulent L. major. Treating these mice with a neutralizing anti-TNF antibody led to partial but not complete inhibition of the resistant state, which suggests that factors other than TNF and gamma interferon contribute to resistance to L. major. PMID:1906844

  20. Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

    Science.gov (United States)

    Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

    2018-05-01

    Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  1. Trial Characteristics as Contextual Factors when Evaluating Targeted Therapies in Patients with Psoriatic Disease

    DEFF Research Database (Denmark)

    Ballegaard, Christine; Jørgensen, Tanja S; Skougaard, Marie

    2018-01-01

    (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the two psoriatic conditions combined by using drug retention as common outcome, and separately by using ACR20 for PsA and PASI75 for psoriasis. We explored potential effect modification of trial...... characteristics in stratified and meta-regression analyses. Odds ratios (OR) were calculated and compared among the trial eligibility criteria via the Ratio of Odds Ratios (ROR). RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons, 17,737 patients) were eligible. Overall retention was OR 2.16 (1.70 to 2.......75) with higher odds for PsA trials compared with psoriasis trials (ROR = 2.55 [1.64 to 3.97]). The eligibility criteria "targeted therapy history", "minimum required disease duration", "required negative rheumatoid factor", and "required CASPAR criteria" were of importance for achieving ACR20 in PsA...

  2. Factors associated with non-adherence to highly active antiretroviral therapy in Nairobi, Kenya

    Directory of Open Access Journals (Sweden)

    Wakibi Samwel N

    2011-12-01

    Full Text Available Abstract Background Antiretroviral therapy (ART requires high-level (> 95% adherence. Kenya is rolling out ART access programmes and, issue of adherence to therapy is therefore imperative. However, published data on adherence to ART in Kenya is limited. This study assessed adherence to ART and identified factors responsible for non adherence in Nairobi. Methods This is a multiple facility-based cross-sectional study, where 416 patients aged over 18 years were systematically selected and interviewed using a structured questionnaire about their experience taking ART. Additional data was extracted from hospital records. Patients were grouped into adherent and non-adherent based on a composite score derived from a three questions adherence tool developed by Center for Adherence Support Evaluation (CASE. Multivariate regression model was used to determine predictors of non-adherence. Results Overall, 403 patients responded; 35% males and 65% females, 18% were non-adherent, and main (38% reason for missing therapy were being busy and forgetting. Accessing ART in a clinic within walking distance from home (OR = 2.387, CI.95 = 1.155-4.931; p = 0.019 and difficulty with dosing schedule (OR = 2.310, CI.95 = 1.211-4.408, p = 0.011 predicted non-adherence. Conclusions The study found better adherence to HAART in Nairobi compared to previous studies in Kenya. However, this can be improved further by employing fitting strategies to improve patients' ability to fit therapy in own lifestyle and cue-dose training to impact forgetfulness. Further work to determine why patients accessing therapy from ARV clinics within walking distance from their residence did not adhere is recommended.

  3. An examination of human factors in external beam radiation therapy: Findings and implications

    International Nuclear Information System (INIS)

    Henriksen, K.; Kaye, R.D.; Jones, R.E. Jr.; Morisseau, D.S.; Persensky, J.J.

    1994-01-01

    To better understand the contributing factors to human error in external beam radiation therapy, the US Nuclear Regulatory Commission has undertaken a series of human factors evaluations. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation technologists, conducted visits to 24 radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was initially performed to guide subsequent evaluations in the areas of human-system interfaces, procedures, training and qualifications, and organizational policies and practices. Representative findings and implications for improvement are discussed within the context of a dynamic model which holds that misadministration likely results from the unanticipated interaction of several necessary but singly insufficient conditions

  4. Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

    Science.gov (United States)

    Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

    2016-01-01

    IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

  5. Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.

    Science.gov (United States)

    Tuszynski, Mark H; Yang, Jennifer H; Barba, David; U, Hoi-Sang; Bakay, Roy A E; Pay, Mary M; Masliah, Eliezer; Conner, James M; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H

    2015-10-01

    Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment. To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. Patients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined. Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay. Among 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P < .05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic

  6. The Provision of Psychological Therapy to People with Intellectual Disabilities: An Investigation into Some of the Relevant Factors

    Science.gov (United States)

    Mason, J.

    2007-01-01

    Background: Five factors are proposed as important in influencing the provision of psychological therapy to people with intellectual disabilities (IDs): the perceived effectiveness of psychological therapy, individual clinician competence, service resources (number of trained clinicians), the level of the clients disability and the diagnostic…

  7. Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

    Science.gov (United States)

    Vallecillo, Gabriel; Robles, María José; Torrens, Marta; Samos, Pilar; Roquer, Albert; Martires, Paula K; Sanvisens, Arantza; Muga, Roberto; Pedro-Botet, Juan

    2018-01-02

    Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m 2 (interquartile range [IQR]: 21.2-28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5-20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6-31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m 2 increase odds ratio [OR]: 1.49, 95% CI: 1.27-1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28-1.48) were associated with metabolic syndrome. Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be

  8. Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2017-11-01

    Full Text Available Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT and antivascular endothelial growth factor (VEGF therapy is effective in the management of chronic central serous chorioretinopathy (CSC recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT, fluorescein angiography (FA, and most with indocyanine green angiography (ICGA followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept. Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010 by 4 months after treatment (1.63±1.18 months. Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019. Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in

  9. Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC

    International Nuclear Information System (INIS)

    Langer, Corey J.

    2004-01-01

    Combination chemotherapy regimens have emerged as the standard approach in advanced non-small-cell lung cancer. Meta-analyses have demonstrated a 2-month increase in median survival after platinum-based therapy vs. best supportive care, and an absolute 10% improvement in the 1-year survival rate. Just as importantly, cytotoxic therapy has produced benefits in symptom control and quality of life. Newer agents, including the taxanes, vinorelbine, gemcitabine, and irinotecan, have expanded our therapeutic options in the treatment of advanced non-small-cell lung cancer. Despite their contributions, we have reached a therapeutic plateau, with response rates seldom exceeding 30-40% in cooperative group studies and 1-year survival rates stable between 30% and 40%. It is doubtful that substituting one agent for another in various combinations will lead to any further improvement in these rates. The thrust of current research has focused on targeted therapy, and epidermal growth factor receptor inhibition is one of the most promising clinical strategies. Epidermal growth factor receptor inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux). Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2). Preclinical models have demonstrated synergy for all these agents in combination with either chemotherapy or radiotherapy, leading to great enthusiasm regarding their ultimate contribution to lung cancer therapy. However, serious clinical challenges persist. These include the identification of the optimal dose(s); the proper integration of these agents into popular, established cytotoxic regimens; and the selection of the optimal setting(s) in which

  10. Change Factors in the Process of Cognitive-Behavioural Therapy for Obsessive-Compulsive Disorder.

    Science.gov (United States)

    Schwartz, C; Hilbert, S; Schubert, C; Schlegl, S; Freyer, T; Löwe, B; Osen, B; Voderholzer, U

    2017-05-01

    While there is a plethora of evidence for the efficacy of cognitive-behavioural therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors of the therapeutic process that account for this success are scarce. In the present study, 155 participants with primary OCD were investigated during CBT inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a measure of symptom severity. In addition, the following process change factors were measured: therapeutic relationship, experience of self-esteem during therapy, experience of mastery, problem actualization and clarification. All variables were assessed on a weekly basis for seven weeks. Linear mixed growth curve analyses were conducted to model the decrease of symptoms over time and to analyse whether the change factors predicted symptom reduction. The analyses revealed a linear decrease of symptoms with high inter-individual variation. Results further showed that increase in self-esteem and mastery experiences as well as the initial score on mastery experience and clarification predicted decrease on the Y-BOCS. We conclude that CBT therapists should focus on clarification in the very first sessions, and try to boost self-esteem and self-efficacy, which is related to mastery, throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd. Increase in mastery and self-esteem experiences are associated with symptom decrease in obsessive-compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial score of mastery experiences and problem clarification predict symptom decrease in OCD during CBT. CBT therapists should focus on problem clarification in the very first sessions and try to boost self-esteem and self-efficacy throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Christina [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany); Engenhart-Cabillic, Rita; Vorwerk, Hilke [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre [Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany)

    2017-02-15

    Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed. From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy. PFT data were collected before treatment and 6 weeks, 12 weeks, and 6 months after RT. The influence of patient- and treatment-related factors on PFT was analyzed. Mean forced expiratory volume in 1 s (FEV1) constantly declined during follow-up (p = 0.001). In total, 68% of patients had a reduced FEV1 at 6 months. Mean vital capacity (VC) didn't change during follow-up (p > 0.05). Mean total lung capacity (TLC) showed a constant decline after RT (p = 0.026). At 6 months, 60% of patients showed a decline in VC and 73% in TLC. The mean diffusion capacity for carbon monoxide (DLCO) declined at 6 and 12 weeks, but recovered slightly at 6 months (p < 0.0005). At 6 months, 86% of patients had a reduced DLCO. After treatment, the partial pressure of CO{sub 2} in the blood (pCO{sub 2}) was increased and pO{sub 2} was decreased (p > 0.05). Only the pretreatment PFT classification had a significant influence on the post-RT FEV1. DLCO seems to be the most reliable indicator for lung tissue damage after thoracic RT. Ventilation parameters appear to be less reliable. Concerning patient- or treatment-related factors, no reliable conclusion can be drawn regarding which factors may be relevant. (orig.) [German] Patientenbezogene, therapiebezogene und Lungenfunktionsdaten (''pulmonary function test'', PFT) wurden vor Radiotherapie (RT) und an verschiedenen Nachsorgeterminen nach RT prospektiv gesammelt, um PFT-Veraenderungen sowie Einflussfaktoren nach Hochdosis-Radio(chemo)therapie zu

  12. Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy.

    Science.gov (United States)

    Sugimoto, Mitsushige; Yamaoka, Yoshio

    2009-01-01

    The cure rates of Helicobacter pylori infection by using a combination of a proton pump inhibitor (PPI) and antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of acid inhibition during the treatment. Currently used empirical triple therapies do not reliably produce a > or =80% cure rate on an intention-to-treat basis. Therefore, tailored regimens based on relevant microbiological findings and pharmacogenomics are recommended for attaining an acceptable > or =95% cure rate. Recently, virulence factors of H. pylori, such as cagA and vacA, are reported to be major factors determining the cure rates. Individuals infected with strains with cagA-negative and vacA s2 genotypes have significantly increased risk of eradication failure of H. pylori infection. These virulence factors enhance gastric mucosal inflammation and are associated with the development of peptic ulcer and gastric cancer. H. pylori virulence factors induce proinflammatory cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor (TNF)- which influence mucosal inflammation and/or gastric acid secretion. When physicians select an H. pylori eradication regimen with an acceptable cure rate, they might need to consider H. pylori virulence factors, especially cagA and vacA.

  13. Multi-factor analysis on events related to hematological toxicity in 153Sm-EDTMP palliative therapy for skeletal metastases

    International Nuclear Information System (INIS)

    Zhan Hongwei; Yu Xiaoling; Ye Xiaojuan; Bao Chengkan; Sun Da; He Gangqiang

    2006-01-01

    Objective: To investigate the clinical factors related to hematological toxicity induced by intravenous samarium-153 ethylenediaminetetramethylene phosphonic acid ( 153 Sm-EDTMP) treatment. Methods A total of 206 patients with bony metastases treated with 153 Sm-EDTMP were retrospectively analyzed. Logistic regression (SPSS 10.0 for Windows) and correlation analysis were used to evaluate the factors concerned. Results: Age of the patient, number of bone metastatic lesion, chemotherapy before 153 Sm-EDTMP therapy, concurrent radiotherapy and repeat-times of 153 Sm-EDTMP treatments were found the individual factors related to hematological toxicity. Chemotherapy before 153 Sm-EDTMP, concurrent radiotherapy, medication for normal blood counting and repeat-times of 153 Sm-EDTMP treatments were the hematological toxicity factors in multi-factor analysis. Conclusion: In 153 Sm-EDTMP therapy, several factors were found related to hematological toxicity suggesting more attention be paid to the change of blood cell counting after the palliative therapy. (authors)

  14. [Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].

    Science.gov (United States)

    Aguilar Del Rey, Francisco Javier; García Portales, Rosa; Haro Liger, Manuel; Rodríguez Andreu, José; Casals Sánchez, José Luis; Pérez González, Rita

    2016-07-15

    To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  15. Factors affecting responses of infants with respiratory distress syndrome to exogenous surfactant therapy.

    Science.gov (United States)

    Ho, N K

    1993-02-01

    Approximately 20% to 30% of infants with respiratory distress syndrome (RDS) do not respond to surfactant replacement therapy. Unfortunately there is no uniform definition of 'response' or 'non-response' to surfactant therapy. Response was based on improvement in a/A PO2 and/or mean airway pressure (MAP) by some and on improvement in FIO2 and/or MAP by others. Even the point of time at which evaluation of response was done is different in various reports. There is an urgent need to adopt an uniform definition. Most premature babies are surfactant deficient which is the aetiological factor of RDS. Generally good antenatal care and perinatal management are essential in avoidance of premature birth. Babies with lung hypoplasia and who are extremely premature (less than 24 weeks of gestation) do not respond well to exogenous surfactant replacement because of structural immaturity. Prompt management of asphyxiated birth and shock are necessary as there may be negative response to surfactant replacement. Foetal exposure to glucocorticoids improves responsiveness to postnatal administration of surfactant. Antenatal steroid therapy has become an important part of management of RDS with surfactant replacement. The premature lungs with high alveolar permeability tend to develop pulmonary oedema. With the presence of plasma-derived surfactant inhibitors, the response to exogenous surfactant may be affected. These inhibitors may also be released following ventilator barotrauma. The standard of neonatal intensive care such as ventilatory techniques has an important bearing on the outcome of the RDS babies.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Impact factor, eigenfactor, article influence, scopus SNIP, and SCImage journal rank of occupational therapy journals.

    Science.gov (United States)

    Brown, Ted; Gutman, Sharon A

    2018-05-18

    Journals are currently assessed and ranked using a number of different quantitative performance metrics. To compare and correlate the publication metrics of English-language occupational therapy journals published in 2015. Bibliometric data was sourced for 14 English-language occupational therapy journals including the Journal Citations Report (JCR) 2-year impact factor (IF), Eigenfactor Score (EFS), Article Influence Score (AIS), Scopus Source Normalized Impact per Paper (SNIP), Scopus Citescore, and SCImago Journal Rank (SJR) score. The JCR, Scopus, and SJR 2015 bibliometric data were correlated. The top six English-language occupational therapy journals in relation to JCR IF, EFS, AIS, SNIP, Citescore, SJR score, and SJR IIF were AJOT, AOTJ, POPT, CJOT, SJOT, and BJOT. JCR IF, EFS, JCR AIS, SNIP, Citescore, SJR score and SJR IIF were all significantly correlated with coefficients ranging from 0.751 to 0.961 (p article rankings rather than the singular use of IF scores that currently and frequently occurs in many jurisdictions.

  17. Delaying ACL reconstruction and treating with exercise therapy alone may alter prognostic factors for 5-year outcome

    DEFF Research Database (Denmark)

    Filbay, Stephanie R; Roos, Ewa M; Frobell, Richard B

    2017-01-01

    , body mass index, preinjury activity level, education and smoking. RESULTS: For all participants (n=118), graft/contralateral ACL rupture, non-ACL surgery and worse baseline 36-item Short-Form Mental Component Scores were associated with worse outcomes. Treatment with exercise therapy alone......AIM: Identify injury-related, patient-reported and treatment-related prognostic factors for 5-year outcomes in acutely ACL-ruptured individuals managed with early reconstruction plus exercise therapy, exercise therapy plus delayed reconstruction or exercise therapy alone. METHODS: Exploratory...... was a prognostic factor for less knee symptoms compared with early reconstruction plus exercise therapy (regression coefficient 10.1, 95% CI 2.3 to 17.9). Baseline meniscus lesion was associated with worse sport/recreation function (-14.4, 95% CI -27.6 to -1.3) and osteochondral lesions were associated with worse...

  18. Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Sally K. da Silva

    2018-06-01

    Full Text Available Objective: To correlate neurotrophic factors – brain-derived neurotrophic factor (BDNF, glial cell line-derived neurotrophic factor (GDNF, and beta-nerve growth factor (beta-NGF – and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD undergoing cognitive-behavioral therapy (CBT. Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

  19. Strengthening the systemic ties that bind: integrating common factors into marriage and family therapy curricula.

    Science.gov (United States)

    Karam, Eli A; Blow, Adrian J; Sprenkle, Douglas H; Davis, Sean D

    2015-04-01

    Specific models guide the training of marriage and family therapists (MFTs) as they offer both structure and organization for both therapists and clients. Learning models may also benefit therapists-in-training by instilling confidence and preventing atheoretical eclecticism. The moderate common factors perspective argues that models are essential, but should not be taught as "the absolute truth," given there is no evidence for relative efficacy of one empirically validated model versus another, and no single model works in all instances. The following article provides a blueprint for infusing a common factors perspective into MFT programmes by reviewing innovations in course design, outlining specific teaching strategies, and highlighting potential implementation challenges. © 2014 American Association for Marriage and Family Therapy.

  20. The factors affecting effectiveness of treatment in phages therapy, mini review

    Directory of Open Access Journals (Sweden)

    Mai Huong eCHATAIN-LY

    2014-02-01

    Full Text Available In recent years, the use of lytic bacteriophages as antimicrobial agents controlling pathogenic bacteria has appeared as a promising new alternative strategy in the face of growing antibiotic resistance which has caused problems in many fields including medicine, veterinary medicine and aquaculture. The use of bacteriophages has numerous advantages over traditional antimicrobials. The effectiveness of phage applications in fighting against pathogenic bacteria depends on several factors such as the bacteriophages/target bacteria ratio, the mode and moment of treatment, environmental conditions (pH, temperature ..., the neutralization of phage and accessibility to target bacteria, amongst others. This report presents these factors and the challenges involved in developing phage therapy applications

  1. Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases

    Science.gov (United States)

    Mori, Shunsuke; Hidaka, Michihiro; Kawakita, Toshiro; Hidaka, Toshihiko; Tsuda, Hiroyuki; Yoshitama, Tamami; Migita, Kiyoshi; Ueki, Yukitaka

    2016-01-01

    Objective Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity. Methods We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups. Results Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia. PMID:27128679

  2. Identifying Predictive Factors for Incident Reports in Patients Receiving Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Elnahal, Shereef M., E-mail: selnaha1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Smith, Koren; Souranis, Annette N.; Briner, Valerie; McNutt, Todd R.; DeWeese, Theodore L.; Wright, Jean L.; Terezakis, Stephanie A. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2016-04-01

    Purpose: To describe radiation therapy cases during which voluntary incident reporting occurred; and identify patient- or treatment-specific factors that place patients at higher risk for incidents. Methods and Materials: We used our institution's incident learning system to build a database of patients with incident reports filed between January 2011 and December 2013. Patient- and treatment-specific data were reviewed for all patients with reported incidents, which were classified by step in the process and root cause. A control group of patients without events was generated for comparison. Summary statistics, likelihood ratios, and mixed-effect logistic regression models were used for group comparisons. Results: The incident and control groups comprised 794 and 499 patients, respectively. Common root causes included documentation errors (26.5%), communication (22.5%), technical treatment planning (37.5%), and technical treatment delivery (13.5%). Incidents were more frequently reported in minors (age <18 years) than in adult patients (37.7% vs 0.4%, P<.001). Patients with head and neck (16% vs 8%, P<.001) and breast (20% vs 15%, P=.03) primaries more frequently had incidents, whereas brain (18% vs 24%, P=.008) primaries were less frequent. Larger tumors (17% vs 10% had T4 lesions, P=.02), and cases on protocol (9% vs 5%, P=.005) or with intensity modulated radiation therapy/image guided intensity modulated radiation therapy (52% vs 43%, P=.001) were more likely to have incidents. Conclusions: We found several treatment- and patient-specific variables associated with incidents. These factors should be considered by treatment teams at the time of peer review to identify patients at higher risk. Larger datasets are required to recommend changes in care process standards, to minimize safety risks.

  3. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults

    Science.gov (United States)

    Beckwith, Noor; Reisner, Sari L.; Zaslow, Shayne; Mayer, Kenneth H.; Keuroghlian, Alex S.

    2017-01-01

    Abstract Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults. Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation. Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist. Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients. PMID:29159310

  4. Identifying Predictive Factors for Incident Reports in Patients Receiving Radiation Therapy

    International Nuclear Information System (INIS)

    Elnahal, Shereef M.; Blackford, Amanda; Smith, Koren; Souranis, Annette N.; Briner, Valerie; McNutt, Todd R.; DeWeese, Theodore L.; Wright, Jean L.; Terezakis, Stephanie A.

    2016-01-01

    Purpose: To describe radiation therapy cases during which voluntary incident reporting occurred; and identify patient- or treatment-specific factors that place patients at higher risk for incidents. Methods and Materials: We used our institution's incident learning system to build a database of patients with incident reports filed between January 2011 and December 2013. Patient- and treatment-specific data were reviewed for all patients with reported incidents, which were classified by step in the process and root cause. A control group of patients without events was generated for comparison. Summary statistics, likelihood ratios, and mixed-effect logistic regression models were used for group comparisons. Results: The incident and control groups comprised 794 and 499 patients, respectively. Common root causes included documentation errors (26.5%), communication (22.5%), technical treatment planning (37.5%), and technical treatment delivery (13.5%). Incidents were more frequently reported in minors (age <18 years) than in adult patients (37.7% vs 0.4%, P<.001). Patients with head and neck (16% vs 8%, P<.001) and breast (20% vs 15%, P=.03) primaries more frequently had incidents, whereas brain (18% vs 24%, P=.008) primaries were less frequent. Larger tumors (17% vs 10% had T4 lesions, P=.02), and cases on protocol (9% vs 5%, P=.005) or with intensity modulated radiation therapy/image guided intensity modulated radiation therapy (52% vs 43%, P=.001) were more likely to have incidents. Conclusions: We found several treatment- and patient-specific variables associated with incidents. These factors should be considered by treatment teams at the time of peer review to identify patients at higher risk. Larger datasets are required to recommend changes in care process standards, to minimize safety risks.

  5. Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

    Science.gov (United States)

    Geres, Alejandra E; Mereshian, Paula Szafryk; Fernández, Silvia; Rey Caro, Daniel Gonzalo; Castro, Ricardo; Podio, Ricardo; Ojeda, Silvia

    2015-12-01

    To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  6. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    International Nuclear Information System (INIS)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho

    2005-01-01

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II ∼ IV or WHO tumor type B2 ∼ C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; ρ = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; ρ = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; ρ = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; ρ = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated

  7. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

    2018-01-01

    Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

  8. Risk Factors for Cataract After Palladium-103 Ophthalmic Plaque Radiation Therapy

    International Nuclear Information System (INIS)

    Finger, Paul T.; Chin, Kimberly J.; Yu Guopei; Patel, Neil S.

    2011-01-01

    Purpose: To examine how tumor characteristics and dose affect cataract development after plaque radiation therapy. Methods and Materials: Three hundred and eighty-four patients were diagnosed with uveal melanoma and treated with palladium-103 ( 103 Pd) plaque radiation therapy. Of these, 282 (74%) inclusion met exclusion criteria for follow-up time, tumor location, and phakic status. Then patient-, ophthalmic-, and radiation-specific factors (patient age, diabetes, hypertension, tumor location, tumor dimensions, and lens dose) were examined (by a Cox proportional regression model) as predictors for the development of radiation-related cataract. Results: Radiation cataract developed in 76 (24%) of patients at a mean follow-up of 39.8 months (range, 1-192). Patients with anteriorly located tumors were noted to have a higher incidence of cataract at 43.0% (43 of 100 patients) vs. 18.1% (33 cataracts per 182 patients) for posteriorly located tumors (p <0.0001). However, multivariate Cox proportional modeling showed that increasing patient age at time of treatment (p for trend = 0.0003) and higher lens dose (p for trend = 0.001) were the best predictors (biomarkers) for radiation cataract. Conclusions: Although anterior tumor location, greater tumor height, and increased patient age (at treatment) were associated with significantly greater risk for radiation cataract, dose to lens was the most significant factor.

  9. Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

    Science.gov (United States)

    Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

    2017-04-01

    Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

  10. Extracorporeal Shockwave Therapy Increases Growth Factor Release from Equine Platelet-Rich Plasma In Vitro

    Directory of Open Access Journals (Sweden)

    Kathryn A. Seabaugh

    2017-12-01

    Full Text Available IntroductionExtracorporeal shockwave therapy (ESWT and platelet-rich plasma (PRP are common treatments for soft tissue injuries in horses. Shockwave triggers cell specific responses to promote healing. Growth factors released from PRP also promote healing. It has been hypothesized that greater growth factor release would amplify the healing process. The combination of ESWT and PRP could promote healing in injured tendons and ligaments in the horse. The objective of this study was to determine if application of shockwaves to PRP samples increases the concentration of transforming growth factor-β1 (TGF-β1 and platelet-derived growth factor ββ (PDGF-ββ released from the platelets in vitro.Materials and methodsPRP was produced from blood drawn from six horses. The PRP from each horse was exposed to the following treatments: (1 positive control (freeze-thaw cycle, (2 untreated negative control, or shockwaves with either (3 a “standard probe” (ESWT-S with a 2 cm focal width and medium energy density or (4 a “power probe” (ESWT-P with a 1 cm focal width and high energy density. After each treatment, the samples were centrifuged, and the supernatant was harvested. The supernatant was then used for growth factor quantification via commercially available ELISA kits for TGF-β1 and PDGF-ββ.ResultsConcentrations of TGF-β1 and PDGF-ββ in PRP that underwent a freeze-thaw cycle were significantly increased compared with all other treatments. Both ESWT-S and ESWT-P resulted in significantly increased TGF-β1 concentrations, 46 and 33%, respectively, when compared with the negative control. Both ESWT-S and ESWT-P resulted in significantly increased PDGF-ββ concentrations, 219 and 190%, respectively, when compared with the negative control.DiscussionThese data indicate that the application of ESWT to PRP increases the expression of growth factors in vitro. This suggests that the combination therapy of local PRP injection followed by ESWT

  11. Factors related to attrition from trauma-focused cognitive behavioral therapy.

    Science.gov (United States)

    Wamser-Nanney, Rachel; Steinzor, Cazzie E

    2017-04-01

    Attrition from child trauma-focused treatments such as Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is common; yet, the factors of children who prematurely terminate are unknown. The aim of the current study was to identify risk factors for attrition from TF-CBT. One hundred and twenty-two children (ages 3-18; M=9.97, SD=3.56; 67.2% females; 50.8% Caucasian) who received TF-CBT were included in the study. Demographic and family variables, characteristics of the trauma, and caregiver- and child-reported pretreatment symptoms levels were assessed in relation to two operational definitions of attrition: 1) clinician-rated dropout, and 2) whether the child received an adequate dose of treatment (i.e., 12 or more sessions). Several demographic factors, number of traumatic events, and children's caregiver-rated pretreatment symptoms were related to clinician-rated dropout. Fewer factors were associated with the adequate dose definition. Child Protective Services involvement, complex trauma exposure, and child-reported pretreatment trauma symptoms were unrelated to either attrition definition. Demographics, trauma characteristics, and level of caregiver-reported symptoms may help to identify clients at risk for premature termination from TF-CBT. Clinical and research implications for different operational definitions and suggestions for future work will be presented. Published by Elsevier Ltd.

  12. Hypoxia-Inducible Factor-1 in Physiological and Pathophysiological Angiogenesis: Applications and Therapies

    Science.gov (United States)

    Zimna, Agnieszka; Kurpisz, Maciej

    2015-01-01

    The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia-inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy. PMID:26146622

  13. Factors affecting adherence to antiretroviral therapy among pregnant women in the Eastern Cape, South Africa.

    Science.gov (United States)

    Adeniyi, Oladele Vincent; Ajayi, Anthony Idowu; Ter Goon, Daniel; Owolabi, Eyitayo Omolara; Eboh, Alfred; Lambert, John

    2018-04-13

    Context-specific factors influence adherence to antiretroviral therapy (ART) among pregnant women living with HIV. Gaps exist in the understanding of the reasons for the variable outcomes of the prevention of mother-to-child transmission (PMTCT) programme at the health facility level in South Africa. This study examined adherence levels and reasons for non-adherence during pregnancy in a cohort of parturient women enrolled in the PMTCT programme in the Eastern Cape, South Africa. This was a mixed-methods study involving 1709 parturient women in the Eastern Cape, South Africa. We conducted a multi-centre retrospective analysis of the mother-infant pair in the PMTCT electronic database in 2016. Semi-structured interviews of purposively selected parturient women with self-reported poor adherence (n = 177) were conducted to gain understanding of the main barriers to adherence. Binary logistic regression was used to determine the independent predictors of ART non-adherence. A high proportion (69.0%) of women reported perfect adherence. In the logistic regression analysis, after adjusting for confounding factors, marital status, cigarette smoking, alcohol use and non-disclosure to a family member were the independent predictors of non-adherence. Analysis of the qualitative data revealed that drug-related side-effects, being away from home, forgetfulness, non-disclosure, stigma and work-related demand were among the main reasons for non-adherence to ART. Non-adherence to the antiretroviral therapy among pregnant women in this setting is associated with lifestyle behaviours, HIV-related stigma and ART side-effects. In order to eliminate mother-to-child transmission of HIV, clinicians need to screen for these factors at every antenatal clinic visit.

  14. Use of Folk Therapy in Taiwan: A Nationwide Cross-Sectional Survey of Prevalence and Associated Factors

    Directory of Open Access Journals (Sweden)

    Chun-Chuan Shih

    2015-01-01

    Full Text Available Background. This study investigates the prevalence of and factors associated with users of folk therapy in Taiwan. Methods. Using data from the 2005 National Health Interview Survey and the National Health Insurance Research Database, we identified 16,750 adults aged 20 years and older. Sociodemographic factors, lifestyle, medical utilization, and health behaviors were compared between people using and not using folk therapy. Adjusted odds ratios (ORs and 95% confidence intervals (CIs of factors associated with folk therapy were analyzed. Results. The one-month prevalence of folk therapy use was 6.8%, which was significantly associated with ages of 30–59 years (OR = 1.98, 95% CI = 1.49–2.63, women (OR = 1.63, 95% CI = 1.40–1.90, nonindigenous population (OR = 1.90, 95% CI = 1.14–3.17, having two or more unhealthy lifestyle habits (OR = 1.51, 95% CI = 1.26–1.81, high density of traditional Chinese medicine (TCM physicians (OR = 1.40, 95% CI = 1.20–1.62, and being ill without receiving medical care in past six months (OR = 2.11, 95% CI = 1.76–2.53. Medical care utilization of TCM and Western medicine were also associated factors for folk therapy. Conclusions. The use of folk therapy is correlated with sociodemographics, lifestyle and health behaviors.

  15. Use of Folk Therapy in Taiwan: A Nationwide Cross-Sectional Survey of Prevalence and Associated Factors

    Science.gov (United States)

    Shih, Chun-Chuan; Huang, Lu-Hsiang; Lane, Hsin-Long; Tsai, Chin-Chuan; Lin, Jaung-Geng; Chen, Ta-Liang; Yeh, Chun-Chieh; Liao, Chien-Chang

    2015-01-01

    Background. This study investigates the prevalence of and factors associated with users of folk therapy in Taiwan. Methods. Using data from the 2005 National Health Interview Survey and the National Health Insurance Research Database, we identified 16,750 adults aged 20 years and older. Sociodemographic factors, lifestyle, medical utilization, and health behaviors were compared between people using and not using folk therapy. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of factors associated with folk therapy were analyzed. Results. The one-month prevalence of folk therapy use was 6.8%, which was significantly associated with ages of 30–59 years (OR = 1.98, 95% CI = 1.49–2.63), women (OR = 1.63, 95% CI = 1.40–1.90), nonindigenous population (OR = 1.90, 95% CI = 1.14–3.17), having two or more unhealthy lifestyle habits (OR = 1.51, 95% CI = 1.26–1.81), high density of traditional Chinese medicine (TCM) physicians (OR = 1.40, 95% CI = 1.20–1.62), and being ill without receiving medical care in past six months (OR = 2.11, 95% CI = 1.76–2.53). Medical care utilization of TCM and Western medicine were also associated factors for folk therapy. Conclusions. The use of folk therapy is correlated with sociodemographics, lifestyle and health behaviors. PMID:26170878

  16. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD, ...

  17. Mutagenesis in sequence encoding of human factor VII for gene therapy of hemophilia

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    B Kazemi

    2009-12-01

    Full Text Available "nBackground: Current treatment of hemophilia which is one of the most common bleeding disorders, involves replacement therapy using concentrates of FVIII and FIX .However, these concentrates have been associated with viral infections and thromboembolic complications and development of antibodies. "nThe use of recombinant human factor VII (rhFVII is effective  for the treatment of patients with  hemophilia A or B, who develop antibodies ( referred as inhibitors against  replacement therapy , because it induces coagulation independent of FVIII and FIX. However, its short half-life and high cost have limited its use. One potential solution to this problem may be the use of FVIIa gene transfer, which would attain continuing therapeutic levels of expression from a single injection. The aim of this study was to engineer a novel hFVII (human FVII gene containing a cleavage site for the intracellular protease and furin, by PCR mutagenesis "nMethods: The sequence encoding light and heavy chains of hFVII, were amplified by using hFVII/pTZ57R and specific primers, separately. The PCR products were cloned in pTZ57R vector. "nResults and discussion: Cloning was confirmed by restriction analysis or PCR amplification using specific primers and plasmid universal primers. Mutagenesis of sequence encoding light and heavy chain was confirmed by restriction enzyme. "nConclusion: In the present study, it was provided recombinant plasmids based on mutant form of DNA encoding light and heavy chains.  Joining mutant form of DNA encoding light chain with mutant heavy chain led to a new variant of hFVII. This variant can be activated by furin and an increase in the proportion of activated form of FVII. This mutant form of hFVII may be used for gene therapy of hemophilia.

  18. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

    Science.gov (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

    1996-08-01

    The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

  19. Factors affecting functional recovery after surgery and hand therapy in patients with Dupuytren's disease.

    Science.gov (United States)

    Engstrand, Christina; Krevers, Barbro; Kvist, Joanna

    2015-01-01

    Prospective cohort study. The evidence of the relationship between functional recovery and impairment after surgery and hand therapy are inconsistent. To explore factors that were most related to functional recovery as measured by DASH in patients with Dupuytren's disease. Eighty-one patients undergoing surgery and hand therapy were consecutively recruited. Functional recovery was measured by the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Explanatory variables: range of motion of the finger joints, five questions regarding safety and social issues of hand function, and health-related quality of life (Euroqol). The three variables "need to take special precautions", "avoid using the hand in social context", and health-related quality of life (EQ-5D index) explained 62.1% of the variance in DASH, where the first variable had the greatest relative effect. Safety and social issues of hand function and quality of life had an evident association with functional recovery. IV. Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  20. Home therapy with continuous infusion of factor VIII after minor surgery or serious haemorrhage.

    Science.gov (United States)

    Varon, D; Schulman, S; Bashari, D; Martinowitz, U

    1996-10-01

    Administration of factor VIII (F VIII) concentrates by continuous infusion is now routinely used at several haemophilia centers but almost exclusively for hospitalized patients. We evaluated various aspects of home therapy with continuous infusion of an immunoaffinity purified F VIII concentrate (Monoclate P®, Armour) in patients who would normally have been treated with high doses in bolus injections or with continuous infusion as in-patients. Twenty haemophilia A patients, eight after minor surgery and 12 for serious haemorrhage, received continuous infusion with undiluted F VIII by a minipump for a mean of 0.9 days in the hospital, followed by 3.3 days at home. Infusion bags were exchanged every 2.5 days. No haemorrhagic complications occurred, and five haemorrhages that had been resistant to treatment with bolus injections responded promptly to the continuous infusion. There were no technical problems and patient compliance and acceptance was good. We find this mode of therapy safe, efficacious and convenient for the patients as well as for the staff.

  1. Predictors of changes in child behaviour following parent management training: Child, context, and therapy factors.

    Science.gov (United States)

    Hagen, Kristine Amlund; Ogden, Terje

    2017-04-01

    This non-randomised study examined a set of predictive factors of changes in child behaviour following parent management training (PMTO). Families of 331 Norwegian girls (26%) and boys with clinic-level conduct problems participated. The children ranged in age from 3 to 12 years (M age = 8.69). Retention rate was 72.2% at post-assessment. Child-, parent- and therapy-level variables were entered as predictors of multi-informant reported change in externalising behaviour and social skills. Behavioural improvements following PMTO amounted to 1 standard deviation on parent rated and ½ standard deviation on teacher rated externalising behaviour, while social skills improvements were more modest. Results suggested that children with higher symptom scores and lower social skills score at pre-treatment were more likely to show improvements in these areas. According to both parent- and teacher-ratings, girls tended to show greater improvements in externalising behaviour and social skills following treatment and, according to parents, ADHD symptomology appeared to inhibit improvements in social skills. Finally, observed increases in parental skill encouragement, therapists' satisfaction with treatment and the number of hours spent in therapy by children were also positive and significant predictors of child outcomes. © 2016 International Union of Psychological Science.

  2. Analysis of influence of dosimetric factors on the outcome of I-131 therapy in patients with hyperthyroidism

    International Nuclear Information System (INIS)

    Knapska-Kucharska, M.; Oszukowska, L.; Makarewicz, J.; Lewinski, A.

    2012-01-01

    The influence of dosimetric factors on the outcome of 131 I therapy has been examined in hyperthyroid patients submitted to 131 I treatment. The following factors - which could have influence on the effects of therapy with radioiodine - were analysed: the goitre volume, the thyroid radioiodine uptake after 24 h, and the effective half-life time of 131 I (EHL). Five hundred (500) randomly selected patients with hyperthyroidism, treated with 131 I, were studied. They were divided into three groups (based on clinical examination, hormonal and immunological tests, thyroid scintigraphy and ultrasound imaging). The study shows that the effectiveness of 131 I therapy depends on the thyroid volume and absorbed dose in all the groups of patients and on the thyroid radioiodine uptake and EHL in patients with a single autonomously functioning thyroid nodule. We have failed to determine the borderline D, distinguishing between effective and ineffective therapy. The treatment outcome can be predicted with approximately 70% accuracy, based on minimal absorbed dose

  3. Evaluation of an anti-tumor necrosis factor therapeutic in a mouse model of Niemann-Pick C liver disease.

    Directory of Open Access Journals (Sweden)

    Melanie Vincent

    2010-09-01

    Full Text Available Niemann-Pick type C (NPC disease is a lysosomal storage disease characterized by the accumulation of cholesterol and glycosphingolipids. The majority of NPC patients die in their teen years due to progressive neurodegeneration; however, half of NPC patients also suffer from cholestasis, prolonged jaundice, and hepatosplenomegaly. We previously showed that a key mediator of NPC liver disease is tumor necrosis factor (TNF α, which is involved in both proinflammatory and apoptotic signaling cascades. In this study, we tested the hypothesis that blocking TNF action with an anti-TNF monoclonal antibody (CNTO5048 will slow the progression of NPC liver disease.Treatment of wild-type C57BL/6 mice with NPC1-specific antisense oligonucleotides led to knockdown of NPC1 protein expression in the liver. This caused classical symptoms of NPC liver disease, including hepatic cholesterol accumulation, hepatomegaly, elevated serum liver enzymes, and lipid laden macrophage accumulation. In addition, there was a significant increase in the number of apoptotic cells and a proliferation of stellate cells. Concurrent treatment of NPC1 knockdown mice with anti-TNF had no effect on the primary lipid storage or accumulation of lipid-laden macrophages. However, anti-TNF treatment slightly blunted the increase in hepatic apoptosis and stellate cell activation that was seen with NPC1 knockdown.Current therapeutic options for NPC disease are limited. Our results provide proof of principle that pharmacologically blocking the TNF-α inflammatory cascade can slightly reduce certain markers of NPC disease. Small molecule inhibitors of TNF that penetrate tissues and cross the blood-brain barrier may prove even more beneficial.

  4. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

    International Nuclear Information System (INIS)

    Hengeveld, P J; Kersten, M J

    2015-01-01

    Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC's capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC's BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916)

  5. What is access to radiation therapy? A conceptual framework and review of influencing factors.

    Science.gov (United States)

    Sundaresan, Puma; Stockler, Martin R; Milross, Christopher G

    2016-02-01

    Optimal radiation therapy (RT) utilisation rates (RURs) have been defined for various cancer indications through extensive work in Australia and overseas. These benchmarks remain unrealised. The gap between optimal RUR and actual RUR has been attributed to inadequacies in 'RT access'. We aimed to develop a conceptual framework for the consideration of 'RT access' by examining the literature for existing constructs and translating it to the context of RT services. We further aimed to use this framework to identify and examine factors influencing 'RT access'. Existing models of health care access were reviewed and used to develop a multi-dimensional conceptual framework for 'RT access'. A review of the literature was then conducted to identify factors reported to affect RT access and utilisation. The electronic databases searched, the host platform and date range of the databases searched were Ovid MEDLINE, 1946 to October 2014 and PsycINFO via OvidSP,1806 to October 2014. The framework developed demonstrates that 'RT access' encompasses opportunity for RT as well as the translation of this opportunity to RT utilisation. Opportunity for RT includes availability, affordability, adequacy (quality) and acceptability of RT services. Several factors at the consumer, referrer and RT service levels affect the translation of this opportunity for RT to actual RT utilisation. 'Access' is a term that is widely used in the context of health service related research, planning and political discussions. It is a multi-faceted concept with many descriptions. We propose a conceptual framework for the consideration of 'RT access' so that factors affecting RT access and utilisation may be identified and examined. Understanding these factors, and quantifying them where possible, will allow objective evaluation of their impact on RT utilisation and guide implementation of strategies to modify their effects.

  6. Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy

    DEFF Research Database (Denmark)

    Woodd, Susannah L; Kelly, Paul; Koethe, John R

    2016-01-01

    BACKGROUND: A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation. METHODS: We...... weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried...... deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests...

  7. Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy.

    Science.gov (United States)

    Wright, Helen L; Bucknall, Roger C; Moots, Robert J; Edwards, Steven W

    2012-03-01

    Biologic drugs have revolutionized the care of RA, but are expensive and not universally effective. To further understand the inflammatory mechanisms underlying RA and identify potential biomarkers predicting response to therapy, we measured multiple cytokine concentrations in SF of patients with inflammatory arthritides (IAs) and, in a subset of patients with RA, correlated this with response to TNF-α inhibition. SF from 42 RA patients and 19 non-RA IA patients were analysed for 12 cytokines using a multiplex cytokine assay. Cytokines were also measured in the plasma of 16 RA patients before and following treatment with anti-TNF-α. Data were analysed using Mann-Whitney U-test, Spearman's rank correlation and cluster analysis with the Kruskal-Wallis test with Dunn's post-test analysis. RA SF contained significantly elevated levels of IL-1β, IL-1ra, IL-2, IL-4, IL-8, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF and TNF-α compared with other IA SF. RA patients who did not respond to anti-TNF therapy had elevated IL-6 in their SF pre-therapy (P < 0.05), whereas responders had elevated IL-2 and G-CSF (P < 0.05). Plasma cytokine concentrations were not significantly modulated by TNF inhibitors, with the exception of IL-6, which decreased after 12 weeks (P < 0.05). Cytokine profiles in RA SF vary with treatment and response to therapy. Cytokine concentrations are significantly lower in plasma than in SF and relatively unchanged by TNF inhibitor therapy. Concentrations of IL-6, IL-2 and G-CSF in SF may predict response to TNF inhibitors.

  8. Efficacy and Safety of Adalimumab in Canadian Patients with Moderate to Severe Crohn’s Disease: Results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn’s DiseaSe (ACCESS Trial

    Directory of Open Access Journals (Sweden)

    Remo Panaccione

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF therapy.

  9. Integrative cardiology-state of the art of mind body therapies for the treatment of cardiovascular disease and risk factors

    Directory of Open Access Journals (Sweden)

    Bernardo Lopez Abel

    2018-02-01

    Full Text Available Mind-body therapies are a heterogeneous group of interventions that seek to improve multiple aspects of somatic health by focusing on interactions between mental factors and physiological functions. There is a growing interest in modern Western culture in these forms of alternative medicine. Most of these therapies exert their effects via stress control. Induction of the relaxation response via neurohormonal, endocrine and immunological pathways may have beneficial effects in a variety of conditions, including oncological, neuropsychiatric and cardiovascular pathologies. Several randomized controlled trials have produced promising results, supporting a complementary role of mind-body therapies for both the prevention and treatment of the most prevalent cardiovascular problems.

  10. Risk Factors for Pelvic Insufficiency Fractures in Locally Advanced Cervical Cancer Following Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ramlov, Anne, E-mail: anraml@rm.dk [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Pedersen, Erik Morre; Røhl, Lisbeth [Department of Radiotherapy, Aarhus University Hospital, Aarhus (Denmark); Worm, Esben [Department of Medical Physics, Aarhus University Hospital, Aarhus (Denmark); Fokdal, Lars; Lindegaard, Jacob Chr. [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Tanderup, Kari [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Department of Medical Physics, Aarhus University Hospital, Aarhus (Denmark)

    2017-04-01

    Purpose: To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). Methods and Materials: We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin and underwent external beam radiation therapy with 45 Gy in 25 fractions (node-negative patients) or 50 Gy in 25 fractions with a simultaneous integrated boost of 60 Gy in 30 fractions (node-positive patients). Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition. Follow-up magnetic resonance imaging was performed routinely at 3 and 12 months after the end of treatment or based on clinical indication. PIF was defined as a fracture line with or without sclerotic changes in the pelvic bones. D{sub 50%} and V{sub 55Gy} were calculated for the os sacrum and jointly for the os ileum and pubis. Patient- and treatment-related factors including dose were analyzed for correlation with PIF. Results: The median follow-up period was 25 months. The median age was 50 years. In 20 patients (20%), a median of 2 PIFs (range, 1-3 PIFs) were diagnosed; half were asymptomatic. The majority of the fractures were located in the sacrum (77%). Age was a significant risk factor (P<.001), and the incidence of PIF was 4% and 37% in patients aged ≤50 years and patients aged >50 years, respectively. Sacrum D{sub 50%} was a significant risk factor in patients aged >50 years (P=.04), whereas V{sub 55Gy} of the sacrum and V{sub 55Gy} of the pelvic bones were insignificant (P=.33 and P=.18, respectively). A dose-effect curve for sacrum D{sub 50%} in patients aged >50 years showed that reduction of sacrum D{sub 50%} from 40 Gy{sub EQD2} to 35 Gy{sub EQD2} reduces PIF risk from 45% to 22%. Conclusions: PIF is common after treatment of LACC and is mainly seen in patients aged >50 years. Our data indicate that PIFs are not related to lymph node

  11. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review.

    Science.gov (United States)

    Govindasamy, Darshini; Ford, Nathan; Kranzer, Katharina

    2012-10-23

    To characterize patient and programmatic factors associated with retention in care during the pre-antiretroviral therapy (ART) period and linkage to ART care. Systematic literature review. An electronic search was conducted on MEDLINE, Global Health, Google Scholar and conference databases to identify studies reporting on predictors, barriers and facilitators of retention in care in the pre-ART period, and linkage to care at three steps: ART-eligibility assessment, pre-ART care and ART initiation. Factors associated with attrition were then divided into areas for intervention. Seven hundred and sixty-eight citations were identified. Forty-two studies from 12 countries were included for review, with the majority from South Africa (16). The most commonly cited category of factors was transport costs and distance. Stigma and fear of disclosure comprised the second most commonly cited category of factors followed by staff shortages, long waiting times, fear of drug side effects, male sex, younger age and the need to take time off work. This review highlights the importance of investigating interventions that could reduce transport difficulties. Decentralization, task-shifting and integration of services need to be expedited to alleviate health system barriers. Patient support groups and strategic posttest counselling are essential to assist patients deal with stigma and disclosure. Moreover, well tolerated first-line drugs and treatment literacy programmes are needed to improve acceptance of ART. This review suggests a combination of interventions to retain specific groups at risk for attrition such as workplace programmes for employed patients, dedicated clinic and support programmes for men and younger individuals.

  12. Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

    Science.gov (United States)

    Sugino, Kiminori; Nagahama, Mitsuji; Kitagawa, Wataru; Ohkuwa, Keiko; Uruno, Takashi; Matsuzu, Kenichi; Suzuki, Akifumi; Masaki, Chie; Akaishi, Junko; Hames, Kiyomi Y; Tomoda, Chisato; Ogimi, Yuna; Ito, Koichi

    2018-03-28

    New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

  13. A pilot study of factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy.

    Science.gov (United States)

    Wen, W; Frampton, R; Wright, K; Fattore, S; Shadbolt, B; Perampalam, S

    2016-02-01

    To identify the knowledge and management factors associated with glycaemic control among adults with Type 1 diabetes mellitus treated with insulin pump therapy. A cross-sectional study of adults with Type 1 diabetes mellitus on insulin pump therapy for at least 12 months (n = 50, 18-70 years old) was undertaken between December 2013 and May 2014. A new questionnaire was developed to evaluate participants' knowledge and management related to insulin pump therapy, and were correlated with insulin pump data, HbA1c and frequency of hypoglycaemia. Participants who changed their insulin pump settings when indicated had significantly better glycaemic control than those who did not (P = 0.04). Multivariate logistic regression analysis found that better overall insulin pump therapy management was a significant predictor of better glycaemic control (odds ratio 4.45, 95% confidence interval 1.61-12.3; P = 0.004) after adjusting for potential confounders including age, gender, duration of diabetes and insulin pump therapy. However, overall insulin pump therapy knowledge was not a significant predictor of glycaemic control (P = 0.058). There was no significant association between frequency of hypoglycaemia and insulin pump therapy knowledge or management. We identified some key knowledge and management factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy using a newly designed questionnaire. The pilot study assessed the clinical utility of this evaluation tool, which may facilitate provision of targeted education to insulin pump therapy users to achieve optimal glycaemic control. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  14. [Assessment of factors associated with patients' comprehension of treatment at the start of antiretroviral therapy].

    Science.gov (United States)

    Braga Ceccato, Maria das Graças; Acurcio, Francisco de Assis; Vallano, Antonio; Comini César, Cibele; Crosland Guimarães, Mark Drew

    2009-01-01

    The aim of this study was to evaluate factors associated with patients' comprehension of antiretroviral therapy (ART). Cross-sectional analysis in which patients at 2 HIV/AIDS public referral centers (Belo Horizonte, Brazil) were interviewed after initiating ART. Information was recorded on variables related to the patient's characteristics, the treatment prescribed, and the healthcare professional involved. A score indicating the patients' level of comprehension regarding the medications prescribed was obtained using a latent trait model estimated by the item response theory. A total of 406 patients were interviewed. Mean (SD) age was 35 (10) years, 227 were men (56%), 302 of Afro-American ethnicity (77%), and 213 had education (53%). The regression model determined that 52.25% of the variability of comprehension was explained by the individual's characteristics. Variables associated (Peducation (tablets, and the ART regimen prescribed. Comprehension of information about the ART regimen prescribed varies considerably between individuals. Nonetheless, several factors were found to be associated with the level of understanding: characteristics of the patient (education, clinical severity), characteristics of treatment (daily number of tablets, ART regimen prescribed), and contribution of healthcare professionals (information from physicians and pharmacists). Strategies to reinforce information about ART should be a priority for patients with a low level of understanding.

  15. Development of epidermal growth factor receptor targeted therapy in pancreatic cancer.

    Science.gov (United States)

    Qing, Liu; Qing, Wang

    2018-02-01

    The epidermal growth factor receptor (EGFR) family are a series of important cancer therapeutic targets involved in cancer biology. These genes play an important role in tumor biological characteristics including angiogenesis, cell survival, invasion and glucose metabolism. In recent years, progresses have been achieved upon the cellular and molecular biological characteristics of EGFR and its role in cancer development based on the study of tumor specimens and experimental animal model. EGFR(HER1/ErbB) is overexpressed in over sixty percent of triple-negative breast cancers and occurs in pancreatic, bladder, lung and head-and-neck cancers. Up to now, EGFR inhibitors have been applied in various of cancer, such as lung, breast, bladder and head and neck cancers etc., in which the combination of EGFR inhibitors plus chemotherapeutic agents is now seen as the standard of care for advanced/metastatic pancreatic cancer. For these reasons, EGFR inhibitors and their therapeutic effect for pancreatic cancer is becoming the focus in Laboratory and clinical research. In this paper, research progress of the development of epidermal growth factor receptor targeted therapy in pancreatic cancer is introduced.

  16. Microphthalmia-associated transcription factor (MITF – from Waardenburg syndrome genetics to melanoma therapy

    Directory of Open Access Journals (Sweden)

    Ivan Šamija

    2010-11-01

    Full Text Available Microphthalmia-associated transcription factor (MITF was first discovered as protein coded by gene whose mutations are associated with Waardenburg syndrome. Later, MITF was shown to be key transcription factor regulating melanogenesis. Further studies have shown that in addition to regulating melanogenesis MITF also plays central role in regulation of melanocyte development and survival. MITF gene is amplified in a proportion of melanomas and ectopic MITF expression can transform melanocytes so MITF can function as melanoma “lineage survival” oncogene. Different studies have further revealed MITF’s important but complex role in tumorigenesis and progression of melanoma. As expected from its important role in melanocytes and melanoma MITF is intricately regulated on all the levels from transcription to post-translational modifications. Although complex mechanisms of MITF functioning are still being revealed, MITF already has a valuable role in managing melanoma patients. Immunohistochemical analysis of MITF has shown both diagnostic and prognostic value in patients with melanoma. MITF is also a valuable specific marker for detection of circulating melanoma cells by reverse-transcription – polymerase chain reaction. MITF has recently been investigated as a potential target for melanoma therapy.

  17. Risk factors for death in HIV-infected adult African patients receiving anti-retroviral therapy.

    Science.gov (United States)

    Siika, A M; Wools-Kaloustian, K; Mwangi, A W; Kimaiyo, S N; Diero, L O; Ayuo, P O; Owino-Ong'or, W D; Sidle, J E; Einterz, R M; Yiannoutsos, C T; Musick, B; Tierney, W M

    2010-11-01

    To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART). Retrospective Case-control study. The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya. Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p<0.003). Patients attending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p<0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level <10 grams% were associated with time to death while age, marital status, educational level, employment status and weight were not. Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital.

  18. Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

    Science.gov (United States)

    Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

    2018-04-03

    High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

  19. Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

    Science.gov (United States)

    Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

    2017-01-01

    AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

  20. Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients.

    Science.gov (United States)

    Lechner, Melissa G; Vyas, Chirag M; Hamnvik, Ole-Petter R; Alexander, Erik K; Larsen, P Reed; Choueiri, Toni K; Angell, Trevor E

    2018-04-01

    Thyroid dysfunction during tyrosine kinase inhibitor (TKI) cancer treatment is common, but predisposing risk factors have not been determined. Recommendations for monitoring patients treated with one or multiple TKI and in conjunction with other relevant cancer therapies could be improved. The study objective was to assess the risk factors for new thyroid dysfunction in TKI-treated previously euthyroid cancer patients. A retrospective cohort study of patients with advanced nonthyroidal cancer treated with TKI from 2000 to 2017, having available thyroid function tests showing initial euthyroid status, excluding patients with preexisting thyroid disease or lack of follow-up thyroid function tests. During TKI treatment, patients were classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (TSH >10 mIU/L, low free thyroxine, or requiring thyroid hormone replacement). The timing of thyroid dysfunction and TKI used were assessed. Risk factors for incident hypothyroidism were evaluated using multivariate models. In 538 adult patients included, subclinical hypothyroidism occurred in 71 (13.2%) and overt hypothyroidism occurred in 144 (26.8%) patients with TKI therapy, following a median cumulative TKI exposure of 196 days (interquartile range [IQR] 63.5-518.5 days). The odds of hypothyroidism were greatest during the first six months on a TKI. Median exposure time on the TKI concurrent with thyroid dysfunction in patients treated with only one TKI was 85 days (IQR 38-293.5 days) and was similar to the 74 days (IQR 38-133.3 days) in patients treated previously with other TKI (p = 0.41). Patients who developed hypothyroidism compared to those who remained euthyroid had greater odds of being female (odds ratio = 1.99 [confidence interval 1.35-2.93], p < 0.01), but greater cumulative TKI exposure and greater number of TKI received were not associated with

  1. Adjuvant endocrine therapy after breast cancer: a qualitative study of factors associated with adherence

    Directory of Open Access Journals (Sweden)

    Brett J

    2018-02-01

    Full Text Available Jo Brett,1 Mary Boulton,1 Debbie Fenlon,2 Nick J Hulbert-Williams,3 Fiona M Walter,4 Peter Donnelly,5 Bernadette A Lavery,6 Adrienne Morgan,7 Carolyn Morris,7 Eila K Watson1 1Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, 2College of Human and Health Sciences, Swansea University, Swansea, Wales, 3Department of Psychology, Chester Research Unit for the Psychology of Health, University of Chester, Chester, 4Department of Public Health and Primary Care, University of Cambridge, Cambridge, 5South Devon Healthcare NHS Foundation Trust, Torbay Hospital, Torquay, 6Cancer Services, Oxford University Hospitals Foundation NHS Trust, Oxford, 7Independent Cancer Patients’ Voice, London, UK Introduction: Despite evidence of the efficacy of adjuvant endocrine therapy (AET in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and nonadherence to AET following breast cancer to inform the development of supportive interventions.Methods: Interviews were conducted with 32 women who had been prescribed AET, 2–4 years following their diagnosis of breast cancer. Both adherers (n=19 and nonadherers (n=13 were recruited. The analysis was conducted using the Framework approach.Results: Factors associated with adherence were as follows: managing side effects including information and advice on side effects and taking control of side effects, supportive relationships, and personal influences. Factors associated with nonadherence were as follows: burden of side effects, feeling unsupported, concerns about long-term AET use, regaining normality, including valuing the quality of life over length of life, and risk perception.Conclusion: Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and

  2. Gene expression of osteogenic factors following gene therapy in mandibular lengthening.

    Science.gov (United States)

    Wu, Guoping; Zhou, Bin; Hu, Chunbing; Li, Shaolan

    2015-03-01

    This study investigated the effect of gene therapy on the expression of osteogenic mediators in mandibular distraction osteogenesis rabbits. Bilateral mandibular osteotomies were performed in 45 New-Zealand rabbits. After a latency of 3 days, the mandibles were elongated using distractors with a rate of 0.8 mm/d for 7 days. After the completion of distraction, the rabbits were randomly divided into 5 groups: 2 μg (0.1 μg/μL) of recombinant plasmid pIRES-hVEGF165-hBMP-2, recombinant plasmid pIRES-hBMP2, recombinant plasmid pIRES-hVEGF165, pIRES, and the same volume of normal saline were injected into the distraction gap of groups A, B, C, D, and E, respectively, followed by electroporation. Three animals were killed at the 7th, 14th, and 28th day after gene transfected in different groups, respectively. The lengthened mandibles were harvested and processed for immunohistochemical examinations; the mean optic densities (MODs) and integral optical density of bone morphogenetic protein (BMP-2) and transforming growth factor β1 (TGF-β1)-positive cells were measured by CMIAS-2001A computerized image analyzer. The data were analyzed with SPSS (SPSS Inc, Chicago, IL). Bone morphogenetic protein 2 and TGF-β1 staining was mainly located in inflammatory cells, monocytes, fibroblasts, osteoblasts, osteocytes, and chondrocytes in the distraction zones. Their strongest expression reached to the peak at the seventh day and decreased at the 14th day of consolidation stage; at the 28th day, they expressed weakly. Image analysis results show that, at the seventh day, the expression of BMP-2 in group B (0.26 ± 0.03, 0.36 ± 0.02) was the strongest; there was significant difference among them (P < 0.01), whereas the expression of TGF-β1 in group C (0.38 ± 0.06, 1.05 ± 0.19) is strongest followed by group A (0.34 ± 0.05, 0.95 ± 0.16) and B (0.33 ± 0.07, 0.90 ± 0.19). At every time point, the level of expression of BMP-2 and TGF-β1 in gene therapy groups (groups A, B, and

  3. Effectiveness and Feasibility Associated with Switching to a Second or Third TNF Inhibitor in Patients with Psoriatic Arthritis

    DEFF Research Database (Denmark)

    Kristensen, Lars Erik; Lie, Elisabeth; Jacobsson, Lennart T H

    2016-01-01

    OBJECTIVE: Because new modes of action for the treatment of psoriatic arthritis (PsA) are emerging, it is important to understand the use of switching to a second or third antitumor necrosis factor (anti-TNF) agent. This study investigated drug survival and treatment response rates of patients...... with PsA undergoing second- and third-line anti-TNF therapy. METHODS: Patients with PsA were monitored in a prospective, observational study. Patients who switched anti-TNF therapy once (first-time switchers, n = 217) or twice (second-time switchers, n = 57) between January 2003 and March 2012 were...... studied. American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) good response at 3 and 6 months, as well as drug survival, were reported and further analyzed using the Cox and logistic regression models. RESULTS: Median age for first-time switchers was 47 years and 42% were...

  4. Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy.

    Science.gov (United States)

    Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho

    2015-12-01

    To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (≥50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (≤1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

  5. Risk factors for mortality in a south Indian population on generic antiretroviral therapy.

    Science.gov (United States)

    Rupali, Priscilla; Mannam, Sam; Bella, Annie; John, Lydia; Rajkumar, S; Clarence, Peace; Pulimood, Susanne A; Samuel, Prasanna; Karthik, Rajiv; Abraham, Ooriapadickal Cherian; Mathai, Dilip

    2012-12-01

    Antiretroviral treatment (ART) programs from low-income countries utilizing standardized ART regimens, simplified approaches to clinical decision making and basic lab monitoring have reported high mortality rates. We determined the risk factors for mortality among HIV-infected adults following the initiation of ART from a single center in south India. ART-naive HIV-infected south Indian adults attending the Infectious Diseases clinic in a 2000-bed academic medical center in south India who were initiated on ART (generic, fixed-dose combinations) as per the national guidelines were followed up. Cases (32 patients who died) were compared with age and sex matched controls. Eight-hundred and twenty-two patients were started on ART from January 1, 2000 to December 31, 2008. The cumulative mortality was 6.8% (56/822). Among the cases mean age was 44 years, 18% were women and mean CD4 counts was 107 cells/microl. Among the controls mean age was 41 years, 18% were women and mean CD4 counts were 113 cells/microl. Stavudine based ART was predominant 62.5% in the cases vs 37.5% in the controls, followed by zidovudine based therapy in 31.2% of cases and 43.7% in the controls. Tenofovir based therapy was used in 6.2% of cases vs 18.7% in the controls. The commonest causes of death were drug toxicity 19%, advanced Acquired Immunodeficiency Syndrome (AIDS) in 37%, Immune Reconstitution Inflammatory Syndrome (IRIS) in 16%, non AIDS related deaths in 22% and malignancies 6%. In a univariate analysis, absolute lymphocyte count ART (p=0.001) were significantly associated with mortality. The mortality among our patients was comparable to that reported from other low-income countries. Earlier initiation of ART may reduce the high mortality rates observed.

  6. Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

    Energy Technology Data Exchange (ETDEWEB)

    Chon, Young Eun [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Beom Kyung [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cha, Jihye [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of); Shin, Sung Kwan, E-mail: kaarma@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Do Young, E-mail: dyk1025@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of)

    2011-12-01

    Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

  7. Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

    International Nuclear Information System (INIS)

    Chon, Young Eun; Seong, Jinsil; Kim, Beom Kyung; Cha, Jihye; Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Shin, Sung Kwan; Kim, Do Young

    2011-01-01

    Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

  8. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.

    Science.gov (United States)

    Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K; van Wijk, Albert C; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C; van Gulik, Thomas M; Storm, Gert; Heger, Michal

    2016-01-19

    Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.

  9. Experience in the management of ECMO therapy as a mortality risk factor.

    Science.gov (United States)

    Guilló Moreno, V; Gutiérrez Martínez, A; Romero Berrocal, A; Sánchez Castilla, M; García-Fernández, J

    2018-02-01

    The extracorporeal oxygenation membrane (ECMO) is a system that provides circulatory and respiratory assistance to patients in cardiac or respiratory failure refractory to conventional treatment. It is a therapy with numerous associated complications and high mortality. Multidisciplinary management and experienced teams increase survival. Our purpose is to evaluate and analyse the effect of the learning curve on mortality. Retrospective and observational study of 31 patients, from January 2012 to December 2015. Patients were separated into 2periods. These periods were divided by the establishment of an ECMO protocol. We compared the quantitative variables by performing the Mann-Whitney U test. For the categorical qualitative variables we performed the chi-square test or Fisher exact statistic as appropriate. The survival curve was computed using the Kaplan-Meier method, and the analysis of statistical significance using the Log-rank test. Data analysis was performed with the STATA programme 14. Survival curves show the tendency to lower mortality in the subsequent period (P=0.0601). The overall mortality rate in the initial period was higher than in the subsequent period (P=0.042). In another analysis, we compared the characteristics of the 2groups and concluded that they were homogeneous. The degree of experience is an independent factor for mortality. The application of a care protocol is fundamental to facilitate the management of ECMO therapy. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.

    Science.gov (United States)

    Ryan, K M; Glaviano, A; O'Donovan, S M; Kolshus, E; Dunne, R; Kavanagh, A; Jelovac, A; Noone, M; Tucker, G M; Dunn, M J; McLoughlin, D M

    2017-03-28

    Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

  11. Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-12-15

    To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (> or =50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (< or =1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

  12. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    Science.gov (United States)

    Romero-Velez, Gustavo; Lisker-Cervantes, Andrés; Villeda-Sandoval, Christian I; Sotomayor de Zavaleta, Mariano; Olvera-Posada, Daniel; Sierra-Madero, Juan Gerardo; Arreguin-Camacho, Lucrecia O; Castillejos-Molina, Ricardo A

    2014-01-01

    Objective To assess the prevalence and risk factors of erectile dysfunction (ED) in HIV patients from the HIV clinic of a tertiary referral center in Mexico City. Design Prevalence was obtained from cross-sectional studies, and the International Index of Erectile Function (IIEF), a standardized method, was used to assess ED. Methods A cross-sectional study was performed in the HIV clinic. Participants completed the IIEF to allow ED assessment. Information on demographics, clinical and HIV-related variables was retrieved from their medical records. Results One hundred and nine patients were included, with a mean age of 39.9 ± 8.8 years. ED was present in 65.1% of the individuals. Patients had been diagnosed with HIV for a mean of 92.7 ± 70.3 months and had undergone a mean 56.4 ± 45.5 months of HAART. The only variable associated with ED in the univariate analysis was dyslipidemia, and this association was also found in the multivariate analysis (P = 0.01). Conclusions ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero-Velez G, Lisker-Cervantes A, Villeda-Sandoval CI, Sotomayor de Zavaleta M, Olvera-Posada D, Sierra-Madero JG, Arreguin-Camacho LO, and Castillejos-Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30. PMID:25356298

  13. Factors associated with interest in receiving prison-based methadone maintenance therapy in Malaysia.

    Science.gov (United States)

    Mukherjee, Trena I; Wickersham, Jeffrey A; Desai, Mayur M; Pillai, Veena; Kamarulzaman, Adeeba; Altice, Frederick L

    2016-07-01

    Methadone maintenance therapy (MMT) is crucial for HIV prevention and treatment in people who inject opioids. In Malaysia, a large proportion of the prison population is affected by both HIV and opioid use disorders. This study assessed individual preferences and factors associated with interest in receiving MMT among male prisoners meeting criteria for opioid dependence in Malaysia. A convenience sample of 96 HIV-positive and 104 HIV-negative incarcerated men who met pre-incarceration criteria for opioid dependence was interviewed using a structured questionnaire to examine participant characteristics and attitudes toward MMT. Factors associated with interest in prison-based MMT initiation were identified using logistic regression analysis. Among all participants, 85 (42.5%) were interested in receiving MMT within prison. Independent correlates of interest in prison-based MMT were being previously married (AOR=4.15, 95% CI: 1.15, 15.02), previously incarcerated (AOR=5.68, 95% CI: 1.54, 21.02), depression (AOR=3.66, 95% CI: 1.68, 7.98), daily heroin use in the 30days prior to incarceration (AOR=5.53, 95% CI: 1.65, 18.58), and more favorable attitudes toward MMT (AOR=19.82, 95% CI: 6.07, 64.74). Overall, interest in receiving prison-based MMT was low, and was associated with adverse social, mental health, and drug use consequences. Incarceration provides a unique opportunity to initiate MMT for those who need it, however, optimal scale-up efforts must be systemic and address modifiable factors like improving attitudes toward and motivation for MMT. Informed or shared decision-making tools may be useful in improving expectations and acceptability of MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Correction factors to convert microdosimetry measurements in silicon to tissue in 12C ion therapy.

    Science.gov (United States)

    Bolst, David; Guatelli, Susanna; Tran, Linh T; Chartier, Lachlan; Lerch, Michael L F; Matsufuji, Naruhiro; Rosenfeld, Anatoly B

    2017-03-21

    Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12 C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of

  15. Prehospital factors determining regional variation in thrombolytic therapy in acute ischemic stroke.

    Science.gov (United States)

    Lahr, Maarten M H; Vroomen, Patrick C A J; Luijckx, Gert-Jan; van der Zee, Durk-Jouke; de Vos, Ronald; Buskens, Erik

    2014-10-01

    Treatment rates with intravenous tissue plasminogen activator vary by region, which can be partially explained by organizational models of stroke care. A recent study demonstrated that prehospital factors determine a higher thrombolysis rate in a centralized vs. decentralized model in the north of the Netherlands. To investigate prehospital factors that may explain variation in thrombolytic therapy between a centralized and a decentralized model. A consecutive case observational study was conducted in the north of the Netherlands comparing patients arriving within 4·5 h in a centralized vs. decentralized stroke care model. Factors investigated were transportation mode, prehospital diagnostic accuracy, and preferential referral of thrombolysis candidates. Potential confounders were adjusted using logistic regression analysis. A total of 172 and 299 arriving within 4·5 h were enrolled in centralized and decentralized settings, respectively. The rate of transportation by emergency medical services was greater in the centralized model (adjusted odds ratio 3·11; 95% confidence interval, 1·59-6·06). Also, more misdiagnoses of stroke occurred in the central model (P = 0·05). In postal code areas with and without potential preferential referral of thrombolysis candidates due to overlapping catchment areas, the odds of hospital arrival within 4·5 h in the central vs. decentral model were 2·15 (95% confidence interval, 1·39-3·32) and 1·44 (95% confidence interval, 1·04-2·00), respectively. These results suggest that the larger proportion of patients arriving within 4·5 h in the centralized model might be related to a lower threshold to use emergency services to transport stroke patients and partly to preferential referral of thrombolysis candidates. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

  16. Risk factors for bone loss with prostate cancer in Korean men not receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Sun-Ouck Kim

    2009-04-01

    Full Text Available PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue due to the accelerated bone loss during androgen deprivation therapy (ADT. In addition, a high prostate-specific antigen (PSA level has been reported to be related to bone metabolism. This study assessed the factors associated with osteoporosis in Korean men with non-metastatic prostate cancer before undergoing ADT. MATERIAL AND METHODS: The study enrolled patients admitted for a prostate biopsy because of a high PSA or palpable nodule on a digital rectal examination. We divided the patients (n = 172 according to the results of the biopsy: group I, non-metastatic prostate cancer (n = 42 and group II, benign prostatic hypertrophy (BPH; n = 130. The lumbar bone mineral density (BMD was evaluated using quantitative computed tomography. The demographic, health status, lifestyle, body mass index (BMI, serum testosterone concentration, and disease variables in prostate cancer (Gleason score, clinical stage, and PSA were analyzed prospectively to determine their effect on the BMD. RESULTS: The estimated mean T-score was higher in group I than in group II (-1.96 ± 3.35 vs. -2.66 ± 3.20, but without statistic significance (p = 0.235. The significant factors correlated with BMD in group I were a high serum PSA (ß = -0.346, p = 0.010 and low BMI (ß = 0.345, p = 0.014 in the multiple linear regression model. Also old age (r = -0.481, p = 0.001, a high serum PSA (r = -0.571, p < 0.001, low BMI (r = 0.598, p < 0.001, and a high Gleason’s score (r = -0.319, p = 0.040 were the factors related to BMD in the correlation. The significant factors correlated with BMD in group II were old age (ß = -0.324, p = 0.001 and BMI (ß = 0.143, p = 0.014 in the multiple linear regression model. CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT is a logical first step in the clinical

  17. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

    2003-08-01

    The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

  18. Quality of Life and Its Related Factors of Radiation Therapy Cancer Patients

    International Nuclear Information System (INIS)

    Shin, Ryung Mi; Jung, Won Seok; Oh, Byeong Heon; Jo, Jun Young; Kim, Gi Chul; Choi, Tae Gyu; Lee, Sok Goo

    2011-01-01

    The purpose of this master's thesis is to utilize basic data in order to improve the quality of life of cancer patients who received radiation therapy after analysing related factors that influence patient's quality of life and obtaining information about physical, mental problems of patients. By using a structured questionnaire about various characteristics and forms of support, I carried out a survey targeting 107 patients that experienced radiation therapy at a university hospital in the Daejeon metropolitan area from July 15 to August 15, 2010 and analysed the factors influencing quality of life. In case of pain due to disease, 65.15 and painless 81.87 showed a high grade quality of life. As body weight decreases, the quality of life become lower. When the grade of quality of life according to economic characteristics was compared, all items except treatment period showed a difference (P=0.000). When the score of social support, family support, medical support and self-esteem was low, the mark of quality of life showed respectively 61.71, 68.77, 71.31, and 69.39 on the basis of 128 points. When the score of support form was high, the mark of quality of life showed 90.47, 83.29, 90.40, and 90.36 (P<0.05). When analyzing the correlation between social support, family support, medical support and self-esteem and the degree of quality of life, social support was 0.768, family support 0.596, medical support 0.434, self-esteem 0.516. They indicated the correlation of meaningful quantity statistically (P<0.01). The factors that improved the quality of life were married state, having a job and painless status. As monthly income increases, the quality of life was also much improved (P<0.05). Among the factors related to quality of life, social support and medical support and higher self-esteem scores of the quality of life score increased 0.979 point, 0.508 points and 1.667 point, respectively. In conclusion, the quality of life of cancer patients that received

  19. Quality of Life and Its Related Factors of Radiation Therapy Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ryung Mi; Jung, Won Seok; Oh, Byeong Heon; Jo, Jun Young; Kim, Gi Chul; Choi, Tae Gyu [Dept. of Radiation Oncology, Kyunghee University Medical Center, Seoul (Korea, Republic of); Lee, Sok Goo [Dept. of Preventive Medicine, Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

    2011-03-15

    The purpose of this master's thesis is to utilize basic data in order to improve the quality of life of cancer patients who received radiation therapy after analysing related factors that influence patient's quality of life and obtaining information about physical, mental problems of patients. By using a structured questionnaire about various characteristics and forms of support, I carried out a survey targeting 107 patients that experienced radiation therapy at a university hospital in the Daejeon metropolitan area from July 15 to August 15, 2010 and analysed the factors influencing quality of life. In case of pain due to disease, 65.15 and painless 81.87 showed a high grade quality of life. As body weight decreases, the quality of life become lower. When the grade of quality of life according to economic characteristics was compared, all items except treatment period showed a difference (P=0.000). When the score of social support, family support, medical support and self-esteem was low, the mark of quality of life showed respectively 61.71, 68.77, 71.31, and 69.39 on the basis of 128 points. When the score of support form was high, the mark of quality of life showed 90.47, 83.29, 90.40, and 90.36 (P<0.05). When analyzing the correlation between social support, family support, medical support and self-esteem and the degree of quality of life, social support was 0.768, family support 0.596, medical support 0.434, self-esteem 0.516. They indicated the correlation of meaningful quantity statistically (P<0.01). The factors that improved the quality of life were married state, having a job and painless status. As monthly income increases, the quality of life was also much improved (P<0.05). Among the factors related to quality of life, social support and medical support and higher self-esteem scores of the quality of life score increased 0.979 point, 0.508 points and 1.667 point, respectively. In conclusion, the quality of life of cancer patients that

  20. Anorectal stenosis after treatment with tumor necrosis factor α antibodies: a case series

    Directory of Open Access Journals (Sweden)

    Keegan Denise

    2010-07-01

    Full Text Available Abstract Introduction We identified three patients who developed anorectal stenosis after successful treatment with anti-tumor necrosis factor α (anti-TNF-α agents. Case presentation Two patients, a 24-year-old Irish Caucasian man and a 64-year-old Irish Caucasian woman, developed symptoms attributable to anorectal stenosis four to six weeks after treatment. A further patient, a 25-year-old Irish Caucasian male, presented three years after treatment with anorectal stenosis, having been asymptomatic with his stenosis for the preceding three years. No patients had evidence of active inflammation at time of representation or had previous anal canal surgery. Conclusion Anorectal stenosis in these patients appears to be independent of active inflammation. No other cause of new stenosis could be identified. We postulate that rapid clinical response to anti-TNF-α agents led to aberrant mucosal healing. This in turn led to anorectal stenosis. This is the first report of this complication in association with the use of biologic agents.

  1. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B

    DEFF Research Database (Denmark)

    Miesbach, Wolfgang; Meijer, Karina; Coppens, Michiel

    2018-01-01

    Hemophilia B gene therapy aims to ameliorate bleeding risk and provide endogenous factor IX (FIX) activity/synthesis through a single treatment, eliminating the requirement for FIX concentrate. AMT-060 combines an adeno-associated virus-5 (AAV5) vector with a liver-specific promoter driving expre...

  2. Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

    NARCIS (Netherlands)

    Siefried, Krista J; Mao, Limin; Kerr, Stephen; Cysique, Lucette A; Gates, Thomas M; McAllister, John; Maynard, Anthony; de Wit, John; Carr, Andrew

    2017-01-01

    BACKGROUND: Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. METHODS: Adults on

  3. [The Relationship Between Quality of Life and Psychological and Behavioral Factors in Patients With Heart Failure Following Cardiac Resynchronization Therapy].

    Science.gov (United States)

    Huang, Jing; Fang, Jin-Bo; Zhao, Yi-Heng

    2018-06-01

    While cardiac resynchronization therapy improves the quality of life of patients with heart failure, some psychological and behavioral factors still affect the quality of life of these patients. However, information on the factors that affect the quality of life of these patients is limited. To describe the quality of life and investigate the relationship between quality of life and behavioral and psychological factors such as depression, smoking, drinking, water and sodium restrictions, exercise, and adherence in patients with chronic heart failure following cardiac resynchronization therapy. This cross-sectional study was conducted using the Morisky Medication Adherence Scale, Minnesota Living With Heart Failure Questionnaire, and Cardiac Depression Scale. A convenience sample of 141 patients with heart failure following cardiac resynchronization therapy were recruited from a tertiary academic hospital in Chengdu. The mean overall score of the Minnesota Living With Heart Failure Questionnaire was 30.89 (out of a total possible score of 105). Water restrictions, sodium restrictions, depression, and exercise were all shown to significantly predict quality of life among the participants. This paper describes the quality of life and defines the behavioral factors that affect the quality of life of patients with heart failure following cardiac resynchronization therapy. The findings suggest that nurses should manage and conduct health education for patients in order to improve their quality of life.

  4. Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States

    Directory of Open Access Journals (Sweden)

    Lund JL

    2013-12-01

    Full Text Available Jennifer L Lund,1 Suzanne F Cook,2 Jeffery K Allen,2 Charlotte F Carroll,2 Michael D Kappelman3 1Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 2Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background and aims: Thiopurines, including 6-mercaptopurine (6-MP and azathioprine (AZA, are the mainstay of maintenance therapy for Crohn's disease (CD. However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. Methods: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001–2008 (n=3,657. We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan–Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the “noncontinuers,” we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. Results: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years and individuals with no prior anti-tumor necrosis factor (TNF use were more likely to continue 6-MP/AZA, while those dispensed more (>4 outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39% and 105 (4% individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. Conclusion: Most patients initiating 6-MP

  5. SU-E-T-577: Obliquity Factor and Surface Dose in Proton Beam Therapy

    International Nuclear Information System (INIS)

    Das, I; Andersen, A; Coutinho, L

    2015-01-01

    Purpose: The advantage of lower skin dose in proton beam may be diminished creating radiation related sequalae usually seen with photon and electron beams. This study evaluates the surface dose as a complex function of beam parameters but more importantly the effect of beam angle. Methods: Surface dose in proton beam depends on the beam energy, source to surface distance, the air gap between snout and surface, field size, material thickness in front of surface, atomic number of the medium, beam angle and type of nozzle (ie double scattering, (DS), uniform scanning (US) or pencil beam scanning (PBS). Obliquity factor (OF) is defined as ratio of surface dose in 0° to beam angle Θ. Measurements were made in water phantom at various beam angles using very small microdiamond that has shown favorable beam characteristics for high, medium and low proton energy. Depth dose measurements were performed in the central axis of the beam in each respective gantry angle. Results: It is observed that surface dose is energy dependent but more predominantly on the SOBP. It is found that as SSD increases, surface dose decreases. In general, SSD, and air gap has limited impact in clinical proton range. High energy has higher surface dose and so the beam angle. The OF rises with beam angle. Compared to OF of 1.0 at 0° beam angle, the value is 1.5, 1.6, 1,7 for small, medium and large range respectively for 60 degree angle. Conclusion: It is advised that just like range and SOBP, surface dose should be clearly understood and a method to reduce the surface dose should be employed. Obliquity factor is a critical parameter that should be accounted in proton beam therapy and a perpendicular beam should be used to reduce surface dose

  6. Long-term primary patency prognostic factors after endovascular therapy for acute lower limb ischemia

    International Nuclear Information System (INIS)

    Zhang Di; Gu Jianping; Lou Wensheng; He Xu; Chen Liang; Chen Guoping; Su Haobo; Song Jinhua; Wang Tao

    2012-01-01

    Objective: To assess prognostic factors regarding long-term primary patency for patients who underwent intra-arterial thrombolysis and/or adjuvant endovascular techniques due to acute lower limb ischemia. Methods: Consecutive patients with ALI of the lower extremities treated via interventional methods between January 2005 and June 2010 were identified and reviewed (exclude patient suffered from aortic dissection involved artery of lower extremity or trauma). Analyze the potential variables with univariable analysis and only factors associated with long-term primary patency with a P value less than 0.1 in univariable analysis were introduced into the Cox regression mode. Total long-term primary patency and grouped primary patency were assessed using Kaplan-Meier estimation. Results: The analyzed dataset included 107 limbs treated in 101 patients presenting with ALI (class Ⅰ 15, class Ⅱ A 36, class Ⅱ B to Ⅲ 56, according to Rutherford classification). Eight nine limbs were enrolled in follow-up.The mean followup was 34 months (range: 1 to 53 months). Primary patency at 12, 24 and 36 months was 87%, 68% and 55%, respectively. Multivariable analyses identified patients presenting with diabetes mellitus (P=0.00), PAOD (P<0.02) and thrombolysis time (P<0.02) were associated with primary patency. Compare the patency rate of patients with different thrombolysis time, the results showed that the patency rate of the patients thrombolysis time less than 4 d was higher than those more than 4 c. Conclusions: Interventional therapy remains an effective treatment option for patients presenting with lower extremity ALI. Diabetes mellitus and PAOD negatively affect the rates of limb primary patency. Thrombolysis should be limited to <4 days. (authors)

  7. [Shereshevsky-Turner syndrome: Estrogen replacement therapy and cardiovascular risk factors].

    Science.gov (United States)

    Yevstigneeva, O A; Andreeva, E N; Grigoryan, O R; Volevodz, N N; Melnichenko, G A; Dedov, I I

    To investigate the impact of menopausal hormone therapy (MHT) on the expression of risk factors for cardiovascular events (CVEs) in patients with Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient management using MHT. From 2010 to 2012, a total of 41 patients aged 14 to 35 years with STS were examined in the framework of a prospective observational study. 100 STS case histories in 2000 to 2009 were retrospectively analyzed. The indicators of the so-called cardiometabolic risk, such as body mass index (BMI), lipidogram readings, venous plasma glucose levels, and blood pressure, were estimated in relation to the type of MHT. In the prospective part of the investigation, an angioscan was used to estimate vessel characteristics (stiffness, wall tone, endothelial function (EF)), by using the examination data. 90% of the patients with STS were found to have risk factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female population of the same age), diastolic hypertension (36%; no more than 5% that is not typical for age-matched healthy general female population). In addition to increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg) reduction in diastolic blood pressure by an average of 13% over 24 months, an increase in high density lipoprotein levels by more than 10% over 24 months and also contributedto a decrease in AWS and an improvement in EF. By favorably affecting the EF of vessels and reducing the severity of atherogenic dyslipidemia, MHT potentially enables a reduction in CV risk in patients with STS.

  8. Neurotrophic Factor-Secreting Autologous Muscle Stem Cell Therapy for the Treatment of Laryngeal Denervation Injury

    Science.gov (United States)

    Halum, Stacey L.; McRae, Bryan; Bijangi-Vishehsaraei, Khadijeh; Hiatt, Kelly

    2012-01-01

    Objectives To determine if the spontaneous reinnervation that characteristically ensues after recurrent laryngeal nerve (RLN) injury could be selectively promoted and directed to certain laryngeal muscles with the use of neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while antagonistic reinnervation is inhibited with vincristine (VNC). Study Design Basic science investigations involving primary cell cultures, gene cloning/transfer, and animal experiments. Methods (i.) MSC survival assays were used to test multiple individual NFs in vitro. (ii.) Motoneuron outgrowth assays assessed the trophic effects of identified NF on cranial nerve X-derived (CNX) motoneurons in vitro. (iii.) Therapeutic NF was cloned into a lentiviral vector, and MSCs were tranduced to secrete NF. 60 rats underwent left RLN transection injury, and at 3 weeks received injections of either MSCs (n=24), MSCs secreting NF (n=24), or saline (n=12) into the left thyroarytenoid muscle complex (TA); half of the animals in the MSC groups simultaneously received left posterior cricoarytenoid (PCA) injections of vincristine (VNC) while half the animals received saline. Results (i.) Ciliary-derived neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in culture. (ii.) Addition of CNTF (50 ng/mL) to CN X motoneuron cultures resulted in enhanced neurite outgrowth and branching. (iii.) In the animal model, the injected MSCs fused with the denervated myofibers, immunohistochemistry demonstrated enhanced reinnervation based on motor endplate to nerve contact, and RT-PCR confirmed stable CNTF expression at longest follow-up (4 months) in the CNTF-secreting MSC treated groups. Conclusions MSC therapy may have a future role in selectively promoting and directing laryngeal reinnervation after RLN injury. Level of evidence: NA PMID:22965802

  9. Factors associated with abandonment of therapy by children diagnosed with solid tumors in Peru.

    Science.gov (United States)

    Vasquez, Liliana; Diaz, Rosdali; Chavez, Sharon; Tarrillo, Fanny; Maza, Ivan; Hernandez, Eddy; Oscanoa, Monica; García, Juan; Geronimo, Jenny; Rossell, Nuria

    2018-06-01

    Abandonment of treatment is a major cause of treatment failure and poor survival in children with cancer in low- and middle-income countries. The incidence of treatment abandonment in Peru has not been reported. The aim of this study was to examine the prevalence of and factors associated with treatment abandonment by pediatric patients with solid tumors in Peru. We retrospectively reviewed the sociodemographic and clinical data of children referred between January 2012 and December 2014 to the two main tertiary centers for childhood cancer in Peru. The definition of treatment abandonment followed the International Society of Paediatric Oncology, Paediatric Oncology in Developing Countries, Abandonment of Treatment recommendation. Data from 1135 children diagnosed with malignant solid tumors were analyzed, of which 209 (18.4%) abandoned treatment. Bivariate logistic regression analysis showed significantly higher abandonment rates in children living outside the capital city, Lima (forest; odds ratio [OR] 3.25; P < 0.001), those living in a rural setting (OR 3.44; P < 0.001), and those whose parent(s) lacked formal employment (OR 4.39; P = 0.001). According to cancer diagnosis, children with retinoblastoma were more likely to abandon treatment compared to children with other solid tumors (OR 1.79; P = 0.02). In multivariate regression analyses, rural origin (OR 2.02; P = 0.001) and lack of formal parental employment (OR 2.88; P = 0.001) were independently predictive of abandonment. Treatment abandonment prevalence of solid tumors in Peru is high and closely related to sociodemographical factors. Treatment outcomes could be substantially improved by strategies that help prevent abandonment of therapy based on these results. © 2018 Wiley Periodicals, Inc.

  10. Anti-vascular endothelial growth factor therapy for the treatment of myopic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Tan CS

    2017-09-01

    Full Text Available Colin S Tan,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore; 3Doheny Eye Institute, University of California Los Angeles, CA, USA Abstract: Myopic choroidal neovascularization (CNV is a sight-threatening condition which occurs in eyes with myopia, particularly in those with pathologic myopia. It is the most common cause of CNV among patients younger than 50 years. Hemorrhage and exudation from the CNV lesion may eventually result in scarring or chorioretinal atrophy. While myopic CNV was previously treated with focal laser photocoagulation or photodynamic therapy (PDT, the current treatment of choice is anti-vascular endothelial growth factor (VEGF agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among patients receiving PDT. In addition, the study demonstrated similar visual outcomes in eyes treated on the basis of visual acuity stabilization or disease activity criteria. Other clinical studies have provided evidence for the efficacy of ranibizumab and aflibercept in the treatment of myopic CNV. This review addresses the epidemiology, pathophysiology, and imaging characteristics of myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as compared to laser photocoagulation and PDT. Keywords: myopic choroidal neovascularization, ranibizumab, anti-vascular endothelial growth factor

  11. Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation.

    Science.gov (United States)

    Mariani, Guglielmo; Napolitano, Mariasanta; Dolce, Alberto; Pérez Garrido, Rosario; Batorova, Angelika; Karimi, Mehran; Platokouki, Helen; Auerswald, Günter; Bertrand, Anne-Marie; Di Minno, Giovanni; Schved, Jean F; Bjerre, Jens; Ingerslev, Jorgen; Sørensen, Benny; Ruiz-Saez, Arlette

    2013-02-01

    Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

  12. Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gunnarsson, Orvar, E-mail: orvar.gunnarsson@uphs.upenn.edu [Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, 16 Penn Tower, Philadelphia, PA 19104 (United States); Basaria, Shehzad [Department of Medicine, Section of Men’s Health, Aging and Metabolism, Brigham and Women’s Hospital, Boston, MA 02115 (United States); Gignac, Gretchen A. [Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA 02118 (United States)

    2015-04-22

    Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI), vitamin-D status, bone mineral density (BMD), dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4%) patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications.

  13. The experimental study of CT-guided hepatocyte growth factor gene therapy for cerebral ischemic diseases

    International Nuclear Information System (INIS)

    Zhang Xiaobo; Jin Zhengyu; Li Mingli; Wang Renzhi; Li Guilin; Kong Yanguo; Wang Jianming; Gao Shan; Guan Hongzhi; Wang Detian; Luo Yufeng

    2006-01-01

    Objectives: To investigate the feasibility of CT guided hepatocyte growth factor (HGF) gene therapy for cerebral ischemic diseases. Methods: Human HGF cDNA was ligated to pIRES 2 -EGFP vector. The recombinant plasmid was transfected into the penumbra tissue with liposome, guided by CT perfusion images. After seven days of transfer with recombinant plasmid, the cut sections of rat brain tissues of the treated and control groups were analyzed including immunohistochemistry, vessel count, cerebral blood flow and infarct volume etc. in order to investigate HGF gene expression and biological effect. Results: Enzymatic digestion and electrophoresis confirmed that HGF fragments had been correctly cloned into the space between the BamH I and Sal I sites of pIRES 2 -EGFP. After 7 days of HGF gene transfection, expression of HGF in transfected neurocytes of treated group was observed with immunohistochemistry. The number of vessels in penumbra tissues transfected with HGF vectors and the CBF measured by perfusion CT all were significantly increased than those of the controls (P 2 -EGFP-HGF complexes can transfect the penumbra tissues and definitely express HGF protein. The HGF gene products can stimulate angiogenesis, promote collateral circulation formation and reduce infarct volume in vivo and therefore is beneficial to the treatment of cerebral ischemia. (authors)

  14. Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice

    International Nuclear Information System (INIS)

    Kanbe, Takamasa; Murai, Rie; Mukoyama, Tomoyuki; Murawaki, Yoshiyuki; Hashiguchi, Ko-ichi; Yoshida, Yoko; Tsuchiya, Hiroyuki; Kurimasa, Akihiro; Harada, Ken-ichi; Yashima, Kazuo; Nishimuki, Eiji; Shabana, Noriko; Kishimoto, Yukihiro; Kojyo, Haruhiko; Miura, Kunihiko; Murawaki, Yoshikazu; Kawasaki, Hironaka; Shiota, Goshi

    2006-01-01

    Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRα promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes

  15. Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Gunnarsson, Orvar; Basaria, Shehzad; Gignac, Gretchen A.

    2015-01-01

    Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI), vitamin-D status, bone mineral density (BMD), dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4%) patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications

  16. Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy

    Directory of Open Access Journals (Sweden)

    Orvar Gunnarsson

    2015-04-01

    Full Text Available Background: Androgen deprivation therapy (ADT for prostate cancer (PCa is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI, vitamin-D status, bone mineral density (BMD, dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4% patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications.

  17. Social inclusion as a therapeutic and educational factor in a music therapy setting

    OpenAIRE

    Loss, Felix

    2016-01-01

    Inclusive approaches for children with special needs are applied in both the fields of music therapy and (music) education. In practice, inclusive music therapy groups consist only of children with special needs, whereas an inclusive kindergarten group for example may consist of typical and non-typical children, yet not in an actual therapy setting. Both practices hold explicit benefits for typical and non-typical children, however mutually exclusive of one another. The aim of the study is to...

  18. Unexpected arterial wall and cellular inflammation in patients with rheumatoid arthritis in remission using biological therapy: a cross-sectional study.

    Science.gov (United States)

    Bernelot Moens, Sophie J; van der Valk, Fleur M; Strang, Aart C; Kroon, Jeffrey; Smits, Loek P; Kneepkens, Eva L; Verberne, Hein J; van Buul, Jaap D; Nurmohamed, Michael T; Stroes, Erik S G

    2016-05-21

    Increasing numbers of patients (up to 40 %) with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this also normalizes their cardiovascular risk. Short-term treatment with TNF inhibitors lowers arterial wall inflammation, but not to levels of healthy controls. We investigated whether RA patients in long-term remission are characterized by normalized inflammatory activity of the arterial wall and if this is dependent on type of medication used (TNF-inhibitor versus nonbiological disease-modifying antirheumatic drugs (DMARDs)). Arterial wall inflammation, bone marrow and splenic activity (index of progenitor cell activity) was assessed with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in RA patients in remission (disease activity score (DAS28) 6 months) and healthy controls. We performed ex vivo characterization of monocytes using flow cytometry and a transendothelial migration assay. Overall, arterial wall inflammation was comparable in RA patients (n = 23) in long-term remission and controls (n = 17). However, RA subjects using current anti-TNF therapy (n = 13, disease activity score 1.98[1.8-2.2]) have an almost 1.2-fold higher (18)F-FDG uptake in the arterial wall compared to those using DMARDs (but with previous anti-TNF therapy) (n = 10, disease activity score 2.24[1.3-2.5]), which seemed to be predominantly explained by longer duration of their rheumatic disease in a multivariate linear regression analysis. This coincided with increased expression of pro-adhesive (CCR2) and migratory (CD11c, CD18) surface markers on monocytes and a concomitant increased migratory capacity. Finally, we found increased activity in bone marrow and spleen in RA patients using anti-TNF therapy compared to those with DMARDs and controls. A subset of patients with RA in clinical remission have activated monocytes and increased inflammation in the arterial wall, despite the use of

  19. Factors Affecting the Ability of the Stroke Survivor to Drive Their Own Recovery outside of Therapy during Inpatient Stroke Rehabilitation

    Science.gov (United States)

    Brauer, Sandra G.; Kuys, Suzanne S.; Lord, Matthew; Hayward, Kathryn S.

    2014-01-01

    Aim. To explore factors affecting the ability of the stroke survivor to drive their own recovery outside of therapy during inpatient rehabilitation. Method. One-on-one, in-depth interviews with stroke survivors (n = 7) and their main carer (n = 6), along with two focus groups with clinical staff (n = 20). Data was thematically analysed according to group. Results. Stroke survivors perceived “dealing with loss,” whilst concurrently “building motivation and hope” for recovery affected their ability to drive their own recovery outside of therapy. In addition, they reported a “lack of opportunities” outside of therapy, with subsequent time described as “dead and wasted.” Main carers perceived stroke survivors felt “out of control … at everyone's mercy” and lacked knowledge of “what to do and why” outside of therapy. Clinical staff perceived the stroke survivor's ability to drive their own recovery was limited by the lack of “another place to go” and the “passive rehab culture and environment.” Discussion. To enable the stroke survivor to drive their own recovery outside of therapy, there is a need to increase opportunities for practice and promote active engagement. Suggested strategies include building the stroke survivor's motivation and knowledge, creating an enriched environment, and developing daily routines to provide structure outside of therapy time. PMID:24800104

  20. Factors Affecting the Ability of the Stroke Survivor to Drive Their Own Recovery outside of Therapy during Inpatient Stroke Rehabilitation

    Directory of Open Access Journals (Sweden)

    Xue Wen Eng

    2014-01-01

    Full Text Available Aim. To explore factors affecting the ability of the stroke survivor to drive their own recovery outside of therapy during inpatient rehabilitation. Method. One-on-one, in-depth interviews with stroke survivors (n=7 and their main carer (n=6, along with two focus groups with clinical staff (n=20. Data was thematically analysed according to group. Results. Stroke survivors perceived “dealing with loss,” whilst concurrently “building motivation and hope” for recovery affected their ability to drive their own recovery outside of therapy. In addition, they reported a “lack of opportunities” outside of therapy, with subsequent time described as “dead and wasted.” Main carers perceived stroke survivors felt “out of control … at everyone’s mercy” and lacked knowledge of “what to do and why” outside of therapy. Clinical staff perceived the stroke survivor’s ability to drive their own recovery was limited by the lack of “another place to go” and the “passive rehab culture and environment.” Discussion. To enable the stroke survivor to drive their own recovery outside of therapy, there is a need to increase opportunities for practice and promote active engagement. Suggested strategies include building the stroke survivor’s motivation and knowledge, creating an enriched environment, and developing daily routines to provide structure outside of therapy time.

  1. Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?

    International Nuclear Information System (INIS)

    Koerber, C.; Schneider, P.; Koerber-Hafner, N.; Haenscheid, H.; Reiners, C.

    2001-01-01

    There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT 3 and FT 4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine ''steal phenomenon'' induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules. (orig.)

  2. Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?

    Energy Technology Data Exchange (ETDEWEB)

    Koerber, C.; Schneider, P.; Koerber-Hafner, N.; Haenscheid, H.; Reiners, C. [Wuerzburg Univ. (Germany). Abt. fuer Nuklearmedizin

    2001-09-01

    There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT{sub 3} and FT{sub 4} levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine ''steal phenomenon'' induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules. (orig.)

  3. Analysis of the radiation therapy outcomes and prognostic factors of thymoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Jae Ik; Sym, Sun Jin; Cho, Eun Kyung [Gil Medical Center, Gachon University of Medicine and Science, Incheon (Korea, Republic of)

    2010-11-15

    This retrospective study was performed to evaluate the efficacy of radiation therapy (RT) and to investigate the prognostic factors for thymoma when treated with RT. We analyzed 21 patients with thymoma and also received RT from March 2002 to January 2008. The median follow-up time was 37 months (range, 3 to 89 months). The median patient age was 57 years (range, 24 to 77 years) and the gender ratio of males to females was 4 : 3. Of the 21 patients, complete resections (trans-sternal thymectomy) and R2 resections were performed in 14 and 1 patient, respectively. A biopsy was performed in 6 patients (28.7%). The WHO cell types in the 21 patients were as follows: 1 patient (4.8%) had type A, 10 patients (47.6%) had type B1-3, and 10 patients (47.6%) had type C. Based on Masaoka staging, 10 patients (47.6%) were stage II, 7 patients (33.3%) were stage III, and 4 patients (19.1%) were stage IVa. Three-dimensional RT was administered to the tumor volume (planned target volume), including the anterior mediastinum and the residual disease. The total RT dose ranged from 52.0 to 70.2 Gy (median dose, 54 Gy). Consistent with the WHO criteria, the response rate was only analyzed for the 6 patients who received a biopsy only. The prognostic factors analyzed for an estimate of survival included age, gender, tumor size, tumor pathology, Masaoka stage, the possibility of treatment by performing surgery, the presence of myasthenia gravis, and RT dose. The 3-year overall survival rate (OS) and the progression free survival rate (PFS) were 80.7% and 78.2%, respectively. Among the 10 patients with WHO cell type C, 3 of 4 patients (75%) who underwent a complete resection and 3 of 6 patients (50%) who underwent a biopsy survived. Distant metastasis developed in 4 patients (19.1%). The overall response rate in the 6 patients who received biopsy only were as follows: partial remission in 4 patients (66.7%), stable disease in 1 patient (16.6%), and progressive disease in 1 patient (16

  4. Analysis of the radiation therapy outcomes and prognostic factors of thymoma

    International Nuclear Information System (INIS)

    Lee, Seok Ho; Lee, Kyu Chan; Choi, Jin Ho; Lee, Jae Ik; Sym, Sun Jin; Cho, Eun Kyung

    2010-01-01

    This retrospective study was performed to evaluate the efficacy of radiation therapy (RT) and to investigate the prognostic factors for thymoma when treated with RT. We analyzed 21 patients with thymoma and also received RT from March 2002 to January 2008. The median follow-up time was 37 months (range, 3 to 89 months). The median patient age was 57 years (range, 24 to 77 years) and the gender ratio of males to females was 4 : 3. Of the 21 patients, complete resections (trans-sternal thymectomy) and R2 resections were performed in 14 and 1 patient, respectively. A biopsy was performed in 6 patients (28.7%). The WHO cell types in the 21 patients were as follows: 1 patient (4.8%) had type A, 10 patients (47.6%) had type B1-3, and 10 patients (47.6%) had type C. Based on Masaoka staging, 10 patients (47.6%) were stage II, 7 patients (33.3%) were stage III, and 4 patients (19.1%) were stage IVa. Three-dimensional RT was administered to the tumor volume (planned target volume), including the anterior mediastinum and the residual disease. The total RT dose ranged from 52.0 to 70.2 Gy (median dose, 54 Gy). Consistent with the WHO criteria, the response rate was only analyzed for the 6 patients who received a biopsy only. The prognostic factors analyzed for an estimate of survival included age, gender, tumor size, tumor pathology, Masaoka stage, the possibility of treatment by performing surgery, the presence of myasthenia gravis, and RT dose. The 3-year overall survival rate (OS) and the progression free survival rate (PFS) were 80.7% and 78.2%, respectively. Among the 10 patients with WHO cell type C, 3 of 4 patients (75%) who underwent a complete resection and 3 of 6 patients (50%) who underwent a biopsy survived. Distant metastasis developed in 4 patients (19.1%). The overall response rate in the 6 patients who received biopsy only were as follows: partial remission in 4 patients (66.7%), stable disease in 1 patient (16.6%), and progressive disease in 1 patient (16

  5. Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms.

    Science.gov (United States)

    Yang, Jie; Zhang, Pengcheng; Zhang, Liyuan; Shu, Huazhong; Li, Baosheng; Gui, Zhiguo

    2017-01-01

    In inverse treatment planning of intensity-modulated radiation therapy (IMRT), the objective function is typically the sum of the weighted sub-scores, where the weights indicate the importance of the sub-scores. To obtain a high-quality treatment plan, the planner manually adjusts the objective weights using a trial-and-error procedure until an acceptable plan is reached. In this work, a new particle swarm optimization (PSO) method which can adjust the weighting factors automatically was investigated to overcome the requirement of manual adjustment, thereby reducing the workload of the human planner and contributing to the development of a fully automated planning process. The proposed optimization method consists of three steps. (i) First, a swarm of weighting factors (i.e., particles) is initialized randomly in the search space, where each particle corresponds to a global objective function. (ii) Then, a plan optimization solver is employed to obtain the optimal solution for each particle, and the values of the evaluation functions used to determine the particle's location and the population global location for the PSO are calculated based on these results. (iii) Next, the weighting factors are updated based on the particle's location and the population global location. Step (ii) is performed alternately with step (iii) until the termination condition is reached. In this method, the evaluation function is a combination of several key points on the dose volume histograms. Furthermore, a perturbation strategy - the crossover and mutation operator hybrid approach - is employed to enhance the population diversity, and two arguments are applied to the evaluation function to improve the flexibility of the algorithm. In this study, the proposed method was used to develop IMRT treatment plans involving five unequally spaced 6MV photon beams for 10 prostate cancer cases. The proposed optimization algorithm yielded high-quality plans for all of the cases, without human

  6. Serum C-reactive Protein Levels Demonstrate Predictive Value for Radiographic and Magnetic Resonance Imaging Outcomes in Patients with Active Ankylosing Spondylitis Treated with Golimumab.

    Science.gov (United States)

    Braun, Jürgen; Baraliakos, Xenofon; Hermann, Kay-Geert A; Xu, Stephen; Hsu, Benjamin

    2016-09-01

    Serum C-reactive protein (CRP) associates with radiographic progression in patients with ankylosing spondylitis (AS) untreated with tumor necrosis factor (TNF) antagonists. We assessed correlations between serum CRP and radiographic progression/magnetic resonance imaging (MRI)-detected inflammation after 2 years of anti-TNF therapy. Patients with active AS receiving golimumab (GOL)/placebo through Week 16 (early escape) or Week 24 (crossover by design), followed by GOL through 4 years, had sera/images obtained through Week 208. Lateral spinal radiographs and spinal MRI were scored with the modified Stoke AS Spine Score (mSASSS) and the AS spine MRI activity (ASspiMRI-a) score, respectively. ANOVA assessed differences based on CRP levels and mSASSS progression. The relationships between CRP levels and mSASSS/ASspiMRI-a were assessed by Spearman correlation and logistic regression. Of the randomized GO-RAISE patients, 299 (84.0%) had pre- and posttreatment spinal radiographs. Larger proportions of patients with Week 104 CRP ≥ 0.5 mg/dl (n = 47) versus formation risk. Elevated CRP after 2 years of anti-TNF treatment correlated with greater radiographic progression risk at 4 years. Elevated CRP at baseline or Week 14/Week 24 of anti-TNF treatment weakly predicted subsequent radiographic progression and modestly predicted residual spinal inflammation in patients with AS treated with anti-TNF. Findings are useful regarding new treatment options in patients treated with anti-TNF. ClinicalTrials.gov: NCT00265083.

  7. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    , a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...

  8. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    , a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...... therapy. RESULTS: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette...

  9. Factors Associated with Quality of Life in Chronic Hepatitis C Patients Who Received Interferon Plus Ribavirin Therapy

    Directory of Open Access Journals (Sweden)

    Shu-Chuan Chang

    2008-06-01

    Conclusion: The study found that patients with chronic hepatitis C who received interferon plus ribavirin therapy had poor quality of life during the treatment period. There was significant difference among patients with different financial stress, and a negative relationship between tangible support and hepatitis quality of life. Financial stress and tangible support are predictors of quality of life for all subjects. The results of this study might assist healthcare personnel to comprehend the quality of life and its related factors in patients with chronic hepatitis C treated with antiviral therapy.

  10. Epidermal growth factor receptor inhibition by anti-CD147 therapy in cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Frederick, John W; Sweeny, Larissa; Hartman, Yolanda; Zhou, Tong; Rosenthal, Eben L

    2016-02-01

    Advanced cutaneous squamous cell carcinoma (SCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and epidermal growth factor receptor (EGFR) have been identified as oncologically important targets, but their relationship remains undefined in cutaneous SCC. Multiple cutaneous SCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, and 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150 µg i.p. triweekly). After treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to controls (p CD147 (200 µg/mL) resulted in decreased cell migration for all cell lines, with an average of 43% reduction in closure compared to controls (p CD147 antibody therapy and siRNA mediated reduction in CD147 expression were both found to decrease protein expression of EGFR, which correlated with a reduction in downstream total and phosphorylated protein kinase B (pAKT). Tumor growth in vivo was reduced for both the anti-CD147 treatment group and the SiCD147 group relative to controls. Inhibition and downregulation of CD147 in cutaneous SCC resulted in suppression of the malignant phenotype in vitro and in vivo, which may be mediated in part by an alteration in EGFR expression. As a result, CD147 may serve as a potential therapeutic target for advanced cutaneous SCC. © 2014 Wiley Periodicals, Inc.

  11. Radiation Therapy, Cardiac Risk Factors, and Cardiac Toxicity in Early-Stage Breast Cancer Patients

    International Nuclear Information System (INIS)

    Doyle, John J.; Neugut, Alfred I.; Jacobson, Judith S.; Wang Jian; McBride, Russell; Grann, Alison; Grann, Victor R.; Hershman, Dawn

    2007-01-01

    Purpose: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer. Methods and Materials: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women ≥65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. Results: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. Conclusion: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years

  12. Factors influencing retention in care after starting antiretroviral therapy in a rural South African programme.

    Directory of Open Access Journals (Sweden)

    Tom H Boyles

    2011-05-01

    Full Text Available The prognosis of patients with HIV in Africa has improved with the widespread use of antiretroviral therapy (ART but these successes are threatened by low rates of long-term retention in care. There are limited data on predictors of retention in care, particularly from rural sites.Prospective cohort analysis of outcome measures in adults from a rural HIV care programme in Madwaleni, Eastern Cape, South Africa. The ART programme operates from Madwaleni hospital and seven primary care feeder clinics with full integration between inpatient and outpatient services. Outreach workers conducted home visits for defaulters.1803 adults initiated ART from June 2005 to May 2009. At the end of the study period 82.4% were in active care or had transferred elsewhere, 11.1% had died and 6.5% were lost to follow-up (LTFU. Independent predictors associated with an increased risk of LTFU were CD4 nadir >200, initiating ART as an inpatient or while pregnant, and younger age, while being in care for >6 months before initiating ART was associated with a reduced risk. Independent factors associated with an increased risk of mortality were baseline CD4 count 6 months before initiating ART and initiating ART while pregnant were associated with a reduced risk.Serving a socioeconomically deprived rural population is not a barrier to successful ART delivery. Patients initiating ART while pregnant and inpatients may require additional counselling and support to reduce LTFU. Providing HIV care for patients not yet eligible for ART may be protective against being LTFU and dying after ART initiation.

  13. The epidermal growth factor receptor as a target for gastrointestinal cancer therapy.

    Science.gov (United States)

    Tedesco, Karen L; Lockhart, A Craig; Berlin, Jordan D

    2004-10-01

    The epidermal growth factor receptor (EGFR) is a member of the family of transmembrane protein kinase receptors known as the erbB or HER receptor family. When activated, EGFR phosphorylates and activates other intracellular proteins that affect cell signaling pathways, cellular proliferation, control of apoptosis and angiogenesis. EGFR signaling is best thought of as a network of activating and inactivating proteins with EGFR as the entry point into the network. EGFR overexpression occurs in most GI malignancies and while data are not entirely consistent, EGFR overexpression often confers a poor prognosis in those GI malignancies that have been studied. It often correlates with poorly differentiated histology, more advanced stage and other known poor prognostic markers. The EGFR is a tempting target because of its presence and overexpression on so many tumor types. However, downstream of the EGFR are several proteins that may be activated without EGFR thus allowing blockade to be overcome. Therefore, while blocking the activity of the EGFR protein appears to be a promising anticancer strategy, a simplistic strategy of blocking only EGFR is likely to only impact a minority of patients. It is time for the laboratory and clinical researchers to work closely together to develop this treatment strategy, moving back and forth from clinical to laboratory to best understand how to block this network effectively enough to produce a broader antitumor effect. While multiple methods of targeting the EGFR pathway are under development, including the inhibition of downstream proteins, only two modalities have entered clinical trials in GI malignancies: small molecule inhibitors of the intracellular kinase domain of EGFR and antibodies designed to block the extracellular ligand-binding domain of EGFR. EGFR inhibitors are still experimental in every GI malignancy with the notable exception of cetuximab that is approved for second or third-line therapy of metastatic colorectal

  14. Factors Influencing Enrollment in the Medication Therapy Management Clinic at an Academic Ambulatory Care Clinic.

    Science.gov (United States)

    Shah, Mansi; Tilton, Jessica; Kim, Shiyun

    2016-04-01

    In 2001, the University of Illinois Hospital and Health Sciences System (UI Health) established a pharmacist-run, referral-based medication therapy management clinic (MTMC). Referrals are obtained from any UI Health provider or by self-referral. Although there is a high volume of referrals, a large percentage of patients do not enroll. This study was designed to determine the various factors that influence patient enrollment in the MTMC. This study was a retrospective chart review of demographic and patient variable data during years 2010 and 2011. Disabilities, distance from MTMC, mode of transportation, past medical history, and appointment dates were extracted from the medical records. Results were analyzed using descriptive statistics and logistic regression analysis. A total of 103 referrals were made; however, only 17% of patients remain enrolled in MTMC. The baseline demographics included a mean age of 63 years, 68% female, 70% African American, and 81% English speaking. Patients lived an average of 8 miles from MTMC; most utilized public or government-supplemented transport services; 24% of patients reported some type of disability, most commonly utilizing a walker or a wheelchair. On average, patients were prescribed 13 medications with hypertension (70%), diabetes (56%), and hyperlipidemia (48%) being the most common chronic disease states. The reason for referral included medication management, education, medication reconciliation, and disease state management. Five patients were unable to be contacted to schedule an initial appointment. Additionally, 18 patients failed their scheduled initial appointment and did not reschedule. Logistic regression analysis demonstrated distance traveled for clinic visit, age, and history of hypertension affected the probability of patients showing for their appointments (chi-square = 19.7, P < .001). This study demonstrated that distance from MTMC is the most common barrier in patient enrollment; therefore, strategies

  15. Incidence of pregnancy following antiretroviral therapy initiation and associated factors in eight West African countries

    Science.gov (United States)

    Burgos-Soto, Juan; Balestre, Eric; Minga, Albert; Ajayi, Samuel; Sawadogo, Adrien; Zannou, Marcel D.; Leroy, Valériane; Ekouevi, Didier K.; Dabis, François; Becquet, Renaud

    2014-01-01

    Introduction This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in eight West African countries over a 10-year period. Methods A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, haemoglobin, age, first ART regimen and calendar year. Results Overall 29,425 HIV-infected women aged 33 years in median [Inter Quartile Range: 28–38] contributed for 84,870 women-years of follow-up to this analysis. The crude incidence of first pregnancy (2,304 events) was 2.9 per 100 women-years [95% confidence interval [CI]: 2.7–3.0], the highest rate being reported among women aged 25–29 years: 4.7 per 100 women-years; 95% CI: 4.3–5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4–11.4) and as high as 28.4% (95% CI: 26.3–30.6) among women aged 20–29 years at ART initiation. Conclusion The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world. PMID:25216079

  16. Determination of absorbed dose calibration factors for therapy level electron beam ionization chambers.

    Science.gov (United States)

    McEwen, M R; Williams, A J; DuSautoy, A R

    2001-03-01

    Over several years the National Physical Laboratory (NPL) has been developing an absorbed dose calibration service for electron beam radiotherapy. To test this service, a number of trial calibrations of therapy level electron beam ionization chambers have been carried out during the last 3 years. These trials involved 17 UK radiotherapy centres supplying a total of 46 chambers of the NACP, Markus, Roos and Farmer types. Calibration factors were derived from the primary standard calorimeter at seven energies in the range 4 to 19 MeV with an estimated uncertainty of +/-1.5% at the 95% confidence level. Investigations were also carried out into chamber perturbation, polarity effects, ion recombination and repeatability of the calibration process. The instruments were returned to the radiotherapy centres for measurements to be carried out comparing the NPL direct calibration with the 1996 IPEMB air kerma based Code of Practice. It was found that, in general, all chambers of a particular type showed the same energy response. However, it was found that polarity and recombination corrections were quite variable for Markus chambers-differences in the polarity correction of up to 1% were seen. Perturbation corrections were obtained and were found to agree well with the standard data used in the IPEMB Code. The results of the comparison between the NPL calibration and IPEMB Code show agreement between the two methods at the +/-1% level for the NACP and Farmer chambers, but there is a significant difference for the Markus chambers of around 2%. This difference between chamber types is most likely to be due to the design of the Markus chamber.

  17. Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients

    Directory of Open Access Journals (Sweden)

    Zhiming Lin

    2015-01-01

    Full Text Available Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P=0.005, CRP (AUC = 0.75; P=0.017, and ASDAS (AUC = 0.778, P=0.007 significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P=0.040 significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ2=6.87, P=0.009, and wald χ2=5.171, P=0.023. Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.

  18. Incidence and risk factors of HIV-related non-Hodgkin's lymphoma in the era of combination antiretroviral therapy: a European multicohort study

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Costagliola, Dominique

    2009-01-01

    Incidence and risk factors of HIV-associated non-Hodgkin's lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART).......Incidence and risk factors of HIV-associated non-Hodgkin's lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART)....

  19. Factors associated with esophageal candidiasis and its endoscopic severity in the era of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    So Nishimura

    Full Text Available Candidia esophagitis (CE is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART era.A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI endoscopy were analyzed. Sexual behavior, CD4(+ count, HIV-RNA viral load (VL, history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi's grade I/II or severe (grade III/IV. Of the 733 subjects, 62 (8.46% were diagnosed with CE (mild, n = 33; severe, n = 29. Of them, 56.5% (35/62 had no GI symptoms, 30.6% (19/62 had CD4 + ≥200 cells/μL, and 55.3% (21/38 had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4(+ counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds. Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29 had no GI symptoms and 44.4% (8/18 had no oral candidiasis. Median CD4(+ counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04.Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.

  20. Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Lee, Young Ho; Bae, Sang-Cheol

    2016-11-01

    This study aimed to assess the relative efficacy and safety of biologics and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate response to tumor necrosis factor (TNF) inhibitors. We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with RA that inadequately responds to TNF inhibitors. Four RCTs including 1796 patients met the inclusion criteria. The tocilizumab 8 mg group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA = 0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415) and placebo (SUCRA = 0). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the treatment options. Tocilizumab 8 mg was the second-line non-TNF biologic with the highest performance regarding an early good response based on ACR20 response rate and acceptable safety profile, followed by rituximab, abatacept and tofacitinib in patients with RA and an inadequate response to anti-TNF therapy, and none of these treatments were associated with a significant risk of withdrawal due to adverse events. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  1. Predictive factors of esophageal stenosis associated with tumor regression in radiation therapy for locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Atsumi, Kazushige; Shioyama, Yoshiyuki; Nakamura, Katsumasa

    2010-01-01

    The purpose of this retrospective study was to clarify the predictive factors correlated with esophageal stenosis within three months after radiation therapy for locally advanced esophageal cancer. We enrolled 47 patients with advanced esophageal cancer with T2-4 and stage II-III who were treated with definitive radiation therapy and achieving complete response of primary lesion at Kyushu University Hospital between January 1998 and December 2005. Esophagography was performed for all patients before treatment and within three months after completion of the radiation therapy, the esophageal stenotic ratio was evaluated. The stenotic ratio was used to define four levels of stenosis: stenosis level 1, stenotic ratio of 0-25%; 2, 25-50%; 3, 50-75%; 4, 75-100%. We then estimated the correlation between the esophageal stenosis level after radiation therapy and each of numerous factors. The numbers and total percentages of patients at each stenosis level were as follows: level 1: n=14 (30%); level 2: 8 (17%); level 3: 14 (30%); and level 4: 11 (23%). Esophageal stenosis in the case of full circumference involvement tended to be more severe and more frequent. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. The extent of involved circumference and wall thickness of tumor region were significantly correlated with esophageal stenosis associated with tumor regression in radiation therapy (p=0.0006, p=0.005). For predicting the possibility of esophageal stenosis with tumor regression within three months in radiation therapy, the extent of involved circumference and esophageal wall thickness of the tumor region may be useful. (author)

  2. An analysis of the incidence and related factors for radiation dermatitis in breast cancer patients who receive radiation therapy

    International Nuclear Information System (INIS)

    Lee, Sun Young; Kwon, Hyoung Cheol; Kim, Jung Soo; Lee, Heui Kwan

    2010-01-01

    We analyzed the incidence and related factors of radiation dermatitis; at first, to recognize whether a decrease in radiation dermatitis is possible or not in breast cancer patients who received radiation therapy. Of 338 patients, 284 with invasive breast cancer who received breast conservation surgery with radiotherapy at Chonbuk National University Hospital from January 2007 to June 2009 were evaluated. Patients who also underwent bolus, previous contralateral breast irradiation and irradiation on both breasts were excluded. For patients who appeared to have greater than moderate radiation dermatitis, the incidence and relating factors for radiation dermatitis were analyzed retrospectively. A total of 207 and 77 patients appeared to have RTOG grade 0/1 or above RTOG grade 2 radiation dermatitis, respectively. The factors found to be statistically significant for the 77 patients who appeared to have greater than moderate radiation dermatitis include the presence of lymphocele due to the stasis of lymph and lymph edema which affect the healing disturbance of radiation dermatitis (p=0.003, p=0.001). Moreover, an allergic reaction to plaster due to the immune cells of skin and the activation of cytokine and concomitant hormonal therapy were also statistically significant factors (p=0.001, p=0.025). Most of the breast cancer patients who received radiation therapy appeared to have a greater than mild case of radiation dermatitis. Lymphocele, lymphedema, an allergy to plaster and concomitant hormonal therapy which affect radiation dermatitis were found to be significant factors. Consequently, we should eliminate lymphocele prior to radiation treatment for patients who appear to have an allergic reaction to plaster. We should also instruct patients of methods to maintain skin moisture if they appear to have a greater than moderate case of radiation dermatitis.

  3. Childhood urinary tract infection caused by extended-spectrum β-lactamase-producing bacteria: Risk factors and empiric therapy.

    Science.gov (United States)

    Uyar Aksu, Nihal; Ekinci, Zelal; Dündar, Devrim; Baydemir, Canan

    2017-02-01

    This study investigated risk factors of childhood urinary tract infection (UTI) associated with extended-spectrum β-lactamase (ESBL)-producing bacteria (ESBL-positive UTI) and evaluated antimicrobial resistance as well as empiric treatment of childhood UTI. The records of children with positive urine culture between 1 January 2008 and 31 December 2012 were evaluated. Patients with positive urine culture for ESBL-producing bacteria were defined as the ESBL-positive group, whereas patients of the same gender and similar age with positive urine culture for non-ESBL-producing bacteria were defined as the ESBL-negative group. Each ESBL-positive patient was matched with two ESBL-negative patients. The ESBL-positive and negative groups consisted of 154 and 308 patients, respectively. Potential risk factors for ESBL-positive UTI were identified as presence of underlying disease, clean intermittent catheterization (CIC), hospitalization, use of any antibiotic and history of infection in the last 3 months (P infection in the last 3 months were identified as independent risk factors. In the present study, 324 of 462 patients had empiric therapy. Empiric therapy was inappropriate in 90.3% of the ESBL-positive group and in 4.5% of the ESBL-negative group. Resistance to nitrofurantoin was similar between groups (5.1% vs 1.2%, P = 0.072); resistance to amikacin was low in the ESBL-positive group (2.6%) and there was no resistance in the ESBL-negative group. Clean intermittent catheterization, hospitalization and history of infection in the last 3 months should be considered as risk factors for ESBL-positive UTI. The combination of ampicillin plus amikacin should be taken into consideration for empiric therapy in patients with acute pyelonephritis who have the risk factors for ESBL-positive UTI. Nitrofurantoin seems to be a logical choice for the empiric therapy of cystitis. © 2016 Japan Pediatric Society.

  4. Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis.

    Science.gov (United States)

    Gallego-Pinazo, Roberto; Dolz-Marco, Rosa; Martínez-Castillo, Sebastián; Arévalo, J Fernando; Díaz-Llopis, Manuel

    2013-02-01

    Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

  5. Perspectives for uveitis treatment in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Alla Aleksandrovna Godzenko

    2011-01-01

    Full Text Available The paper describes current approaches to treating uveitis in rheumatic diseases and theoretical backgrounds for using tumor necrosis factor-α (TNF-α inhibitors. The data available in the literature suggest that anti-TNFtherapy is highly effective in relieving and preventing uveitis attacks.

  6. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  7. Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Choy, Hak

    2004-01-01

    There has been a surge of interest in the translation of discoveries in molecular biology into clinically relevant therapies in the field of hematology/oncology. The epidermal growth factor receptor (EGFR) has been a molecular target of significant interest and investigation, and preclinical and clinical studies support a role for targeted therapy in a variety of cancers, including non-small-cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839, IMC-C225, and OSI-774 are the most clinically developed of these compounds. Interestingly, preclinical studies have demonstrated that EGFR inhibitors may have radiation-sensitizing properties, as well as increased cytotoxic activity in combination with chemotherapeutic agents, suggesting a potential role for EGFR inhibitors as an adjunct to the current combined-modality approach for therapy of Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to address the issue of determining the impact of the addition of EGFR inhibitors to the standard combined-modality regimen (chemotherapy/radiation therapy ± surgery) for Stage III NSCLC. This article reviews preclinical and clinical data supporting the role for EGFR inhibitors alone or in combination with chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide an overview of ongoing and proposed clinical studies investigating the potential role for EGFR inhibitors in Stage III NSCLC

  8. Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chiaki Okuse; Hiroshi Yotsuyanagi; Yoshihiko Nagase; Yuhtaro Kobayashi; Kiyomi Yasuda; Kazuhiko Koike; Shiro Iino; Michihiro Suzuki; Fumio Itoh

    2006-01-01

    AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.

  9. Analysis of influence of dosimetric factors on the outcome of I-131 therapy in patients with hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Knapska-Kucharska, M.; Oszukowska, L.; Makarewicz, J. [Department of Nuclear Medecine and Oncological Endocrinology, Province Hospital, Zgierz (Poland); Lewinski, A. [Chair and Department of Endocrinology and Metabolic Diseases, Medical University, Lodz (Poland)

    2012-07-01

    The influence of dosimetric factors on the outcome of {sup 131}I therapy has been examined in hyperthyroid patients submitted to {sup 131}I treatment. The following factors - which could have influence on the effects of therapy with radioiodine - were analysed: the goitre volume, the thyroid radioiodine uptake after 24 h, and the effective half-life time of {sup 131}I (EHL). Five hundred (500) randomly selected patients with hyperthyroidism, treated with {sup 131}I, were studied. They were divided into three groups (based on clinical examination, hormonal and immunological tests, thyroid scintigraphy and ultrasound imaging). The study shows that the effectiveness of {sup 131}I therapy depends on the thyroid volume and absorbed dose in all the groups of patients and on the thyroid radioiodine uptake and EHL in patients with a single autonomously functioning thyroid nodule. We have failed to determine the borderline D, distinguishing between effective and ineffective therapy. The treatment outcome can be predicted with approximately 70% accuracy, based on minimal absorbed dose

  10. Anticoagulation therapy a risk factor for the development of chronic subdural hematoma

    DEFF Research Database (Denmark)

    Aspegren, Oskar P.; Åstrand, Ramona; Lundgren, Maria I.

    2013-01-01

    Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy.......Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy....

  11. Serum Transforming Growth Factor-β1 Change After Neoadjuvant Chemoradiation Therapy Is Associated With Postoperative Pulmonary Complications in Esophageal Cancer Patients Undergoing Combined Modality Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Shao-Lun; Hsu, Feng-Ming; Tsai, Chiao-Ling; Wu, Jian-Kuan [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Lee, Jang-Ming; Huang, Pei-Ming [Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Chih-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Koong, Albert C.; Chang, Daniel T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Chia-Hsien Cheng, Jason, E-mail: jasoncheng@ntu.edu.tw [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China)

    2015-12-01

    Purpose: Our aim was to investigate the association of clinical factors, dosimetric parameters, and biomarkers with postoperative pulmonary complications (PPCs) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated by neoadjuvant concurrent chemoradiation therapy (CCRT) under strict pulmonary dose constraints and esophagectomy. Methods and Materials: We prospectively enrolled 112 patients undergoing trimodality treatment (including radiation therapy [40 Gy], concurrent taxane-/5-fluorouracil-based regimens, and radical esophagectomy) for ESCC. A PPC was defined as pneumonia or acute respiratory distress syndrome within 30 days after surgery. Serum samples were collected before and within 1 month after CCRT. The association of serum biomarkers with PPCs was detected by proximity ligation assay (PLA) and verified by enzyme-linked immunosorbent assay. Associations of clinical factors, lung dosimetric parameters, and biomarkers with PPC were tested statistically. Results: Thirty-three patients (29.5%) had PPCs. None of the dosimetric parameters was associated with PPCs. Preoperative functional vital capacity (FVC) was significantly associated with PPCs (P=.004). Of the 15 PLA-screened biomarkers, posttreatment transforming growth factor-β1 (TGF-β1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-β1 concentration (−11,310 vs −5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-β1 concentration (−37.4% vs −25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-β1 >7040 pg/mL (P=.014) were independent factors associated with PPCs. Conclusions: Preoperative FVC and decrease in serum TGF-β1 level after dose-limited CCRT to the lung are associated with the development of PPCs.

  12. Application of stem cell/growth factor system, as a multimodal therapy approach in regenerative medicine to improve cell therapy yields.

    Science.gov (United States)

    Pourrajab, Fatemeh; Babaei Zarch, Mojtaba; Baghi Yazdi, Mohammad; Rahimi Zarchi, Abolfazl; Vakili Zarch, Abbas

    2014-04-15

    Stem cells hold a great promise for regenerative medicine, especially for replacing cells in infarcted organ that hardly have any intrinsic renewal capacity, including heart and brain. Signaling pathways that regulate pluripotency or lineage-specific gene and protein expression have been the major focus of stem cell research. Between them, there are some well known signaling pathways such as GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines may regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes or accentuate synergistic compliance. For example, contributing factors in the progression of heart failure are both the loss of cardiomyocytes after myocardial infarction, and the absence of an adequate endogenous repair signaling. Combining cell engraftment with therapeutic signaling factor delivery is more exciting in terms of host progenitor/donor stem cell survival and proliferation. Thus stem cell-based therapy, besides triggering signaling pathways through GF/GFR systems can become a realistic option in regenerative processes for replacing lost cells and reconstituting the damaged organ, as before. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Integration of anti-vascular endothelial growth factor therapies with cytotoxic chemotherapy in the treatment of colorectal cancer.

    Science.gov (United States)

    Oliveira, Suilane Coelho Ribeiro; Machado, Karime Kalil; Sabbaga, Jorge; Hoff, Paulo M

    2010-01-01

    Colorectal cancer is one of the most prevalent malignancies worldwide, and its incidence continues to rise. The treatment for advanced colorectal cancer has significantly evolved in the last decade, with the addition of a number of new therapeutic agents; however, 5-fluorouracil remains at the core of most therapeutic approaches for this disease. Novel therapies targeting specific pathways have been developed for this disease, and the vascular endothelial growth factor ligand and receptor have been of particular interest. The blockade of what is considered the main angiogenic pathway is considered one of the main advances in cancer treatment. The aim of this article is to review the current status of the integration between anti-vascular endothelial growth factor therapies and cytotoxic chemotherapy, investigate what is known about development of resistance, and to explore new options of antiangiogenic treatments currently in late phases of development against colorectal cancer.

  14. Usefulness of radiation treatment planning allpied respiration factor for streotatic body radiation therapy in the lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sung Pil; Kim, Tae Hyung; So, Woon Young; Back, Geum Mun [Dept. of Medical Health Science, Graduate School, Kangwon National University, Chuncheon (Korea, Republic of)

    2016-12-15

    We are evaluated the usefulness of radiation treatment planning applied respiration factor for stereotactic body radiation therapy in the lung cancer. Four dimensional computed tomography images were obtained in 10 patients with lung cancer. The radiation treatment plans were established total lung volume according to respiration images (new method) and conventional method. We was analyzed in the lung volume, radiation absorbed dose of lung and main organs (ribs, tracheobronchus, esophagus, spinal cord) around the tumor, respectively. We were confirmed that lung volume and radiation absorbed dose of lung and main organs around the tumor deference according to applied respiration. In conclusion, radiation treatment planning applied respiration factor seems to be useful for stereotactic body radiation therapy in the lung cancer.

  15. Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department.

    Science.gov (United States)

    Bischoff, Sebastian; Walter, Thomas; Gerigk, Marlis; Ebert, Matthias; Vogelmann, Roger

    2018-01-26

    The aim of this study was to identify clinical risk factors for antimicrobial resistances and multidrug resistance (MDR) in urinary tract infections (UTI) in an emergency department in order to improve empirical therapy. UTI cases from an emergency department (ED) during January 2013 and June 2015 were analyzed. Differences between patients with and without resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz), Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher's exact tests. Results were used to identify risk factors with logistic regression modelling. Susceptibility rates were analyzed in relation to risk factors. One hundred thirty-seven of four hundred sixty-nine patients who met the criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5% of these. Overall susceptibility was less than 85% for standard antimicrobial agents. Logistic regression identified residence in nursing homes, male gender, hospitalization within the last 30 days, renal transplantation, antibiotic treatment within the last 30 days, indwelling urinary catheter and recurrent UTI as risk factors for MDR or any of these resistances. For patients with no risk factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%, Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%, Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively. We identified several risk factors for resistances and MDR in UTI. Susceptibility towards antimicrobials depends on these risk factors. With no risk factor cephalosporins seem to be the best choice for empiric therapy, but in patients with risk factors the beta-lactam penicillin Piperacillin with Tazobactam

  16. Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.

    Science.gov (United States)

    Chayama, Kazuaki; Hayes, C Nelson; Yoshioka, Kentaro; Moriwaki, Hisataka; Okanoue, Takashi; Sakisaka, Shotaro; Takehara, Tetsuo; Oketani, Makoto; Toyota, Joji; Izumi, Namiki; Hiasa, Yoichi; Matsumoto, Akihiro; Nomura, Hideyuki; Seike, Masataka; Ueno, Yoshiyuki; Yotsuyanagi, Hiroshi; Kumada, Hiromitsu

    2011-04-01

    Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy. We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment. When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%. Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.

  17. Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

    Science.gov (United States)

    Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

    2005-09-01

    Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

  18. The epidermal growth factor receptor (EGFr) as a target for in situ radiation therapy

    International Nuclear Information System (INIS)

    Vallis, K.A.; Reilly, R.M.

    2003-01-01

    In situ radiation therapy traditionally involves the use of a monoclonal antibody (mAb) directed against a specific tumor-associated antigen and labeled with α-particle emitter such as 131-I. An alternative strategy is to use a low molecular weight peptide rather than a mAb as the carrier molecule. Also, recent evidence shows that radioactive elements that emit Auger electrons may be useful for inducing receptor/cell-specific cytotoxicity. Auger electrons provide low energy emissions (<10-20 keV). Although they have a short range in tissue (a few mm), Auger electrons have a high rate of energy deposition that is comparable to high linear energy transfer radiation such as -particles. Human epidermal growth factor (hEGF) is a natural peptide ligand for EGFr, which is frequently overexpressed in breast cancer. EGF is rapidly internalized and translocated to the cell nucleus following binding to EGFr. We are developing a strategy of EGF conjugated to an Auger electron-emitting radionuclide, 111-In, as a treatment for EGFr-overexpressing breast cancers. This strategy has several advantages over the mAb approach, as EGF is an endogenous peptide and should not be immunogenic. Also, its small molecular size should facilitate extravasation and tumor penetration. We have shown that 111In-hEGF is highly and selectively radiotoxic to MDA-MB-468 human breast cancer cells overexpressing EGFr but was not radiotoxic to MCF-7 breast cancer cells with a 100-fold lower level of EGFr expression. We have also demonstrated that 111-In-hEGF was greater than 80-fold more potent on a molar concentration basis at inhibiting the growth of MDA-MB-468 breast cancer cells than paclitaxel (IC50 70 pM vs. 6 nM respectively) and greater than 400-fold more potent than doxorubicin (IC50 20 nM). We have evaluated the therapeutic efficacy of 111-In-hEGF in athymic mice implanted subcutaneously with MDA-MB-468 breast cancer xenografts. Tumour growth was strongly inhibited following administration of

  19. Integrated cancer therapy combined radiotherapy and immunotherapy. The challenge of using Gc protein-derived macrophage activating factor (GcMAF) as a key molecule

    International Nuclear Information System (INIS)

    Uto, Yoshihiro; Hori, Hitoshi

    2013-01-01

    Radiation oncologists know the conflict between radiotherapy and immunotherapy, but now challenged trails of the integrative cancer therapies combined radiation therapy and various immunoreaction/immune therapies begin. We therefore review the recent results of basic research and clinical trial of the integrated cancer therapies which combined radiotherapy and various immune therapies/immunoreaction, and the challenged studies of combined use of radiotherapy and our developed cancer immunotherapy using serum GcMAF which is human serum containing Gc protein-derived macrophage activating factor (GcMAF). (author)

  20. Neurobiological factors as predictors of cognitive-behavioral therapy outcome in individuals with antisocial behavior: a review of the literature.

    Science.gov (United States)

    Cornet, Liza J M; de Kogel, Catharina H; Nijman, Henk L I; Raine, Adrian; van der Laan, Peter H

    2014-11-01

    This review focuses on the predictive value of neurobiological factors in relation to cognitive-behavioral therapy outcome among individuals with antisocial behavior. Ten relevant studies were found. Although the literature on this topic is scarce and diverse, it appears that specific neurobiological characteristics, such as physiological arousal levels, can predict treatment outcome. The predictive value of neurobiological factors is important as it could give more insight into the causes of variability in treatment outcome among individuals with antisocial behavior. Furthermore, results can contribute to improvement in current treatment selection procedures and to the development of alternative treatment options. © The Author(s) 2013.

  1. Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy.

    Science.gov (United States)

    Schmidt, M; Hochhaus, A; König-Merediz, S A; Brendel, C; Proba, J; Hoppe, G J; Wittig, B; Ehninger, G; Hehlmann, R; Neubauer, A

    2000-10-01

    Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-alpha) treatment in CML. Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-alpha therapy and in 47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was then correlated with cytogenetic response to IFN-alpha. IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-alpha therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-alpha, a good response was associated with high IRF4 expression. IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-alpha therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-alpha in CML.

  2. Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Fernanda Vaisman

    2011-01-01

    Full Text Available BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14. The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up. Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014. The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

  3. Tuberculous peritonitis during infliximab therapy

    NARCIS (Netherlands)

    Verhave, J. C.; van Altena, R.; Wijnands, M. I. H.; Roerdink, H. Th. J.

    Reactivation of tuberculosis is a severe side effect of anti-TNF treatment. Especially extrapulmonary forms of tuberculosis may occur, which are difficult to diagnose. The diagnosis may be obtained by a thorough search for Mycobacterium tuberculosis. We describe two patients who developed

  4. Noncompliance with drug therapy of glaucoma: a review about intervening factors

    Directory of Open Access Journals (Sweden)

    Aldemar Nemésio Brandão Vilela de Castro

    2009-09-01

    Full Text Available Glaucoma is defined as an optic neuropathy, characterized for loss of visual field and injury of the optic nerve, being considered as the second cause of blindness in the world, which could be prevented by the use of antiglaucoma eyedrops. The lack of adhesion of the patient to the drug treatment can culminate with loss of the vision. The objective was to revise possible literature data regarding intervening factors for noncompliance and explain estimated rates of noncompliance. A systematic review about the subject was carried out in the period of January to June of 2006. Articles had been searched in two data bases, in the National Library of Medicine (PUBMED and in the Literature Latin American and Caribbean Health Sciences (LILACS using the following keywords: glaucoma, compliance of the patient, noncompliance of the patient, treatment and eyedrops. In PUBMED, 199 articles were collected, written in English and French languages. No article was found in LILACS. Considering the inclusion and exclusion criteria, 27 articles were selected, with 25 originals and two reviews. Twelve possible intervening factors for noncompliance were raised, as well as estimates for rates of noncompliance. The noncompliance rates varied from 4.6% up to 59%. Two factors, forgetfulness and inadequate between-doses interval, had been associated to noncompliance of the drug therapy. The factors race, adverse effects, treatment cost, number of instilled doses, coexisting illnesses and number of eyedrops used, had resulted contradictory, being impossible to affirm that they have contributed for noncompliance. Age, sex, educational level and loss of visual field, had not been associated with noncompliance. The glaucoma patients tended to disregard the drug treatment. The wide variation in noncompliance rates could be an influence from the authors' difficulty to define the noncompliance and the variety of methodologies used to estimate it. More studies are necessary for a

  5. Impact of prognostic factors for postmastectomy radiation therapy of breast cancer patients

    Science.gov (United States)

    Simonov, K. A.; Startseva, Zh. A.; Slonimskaya, E. M.; Velikaya, V. V.

    2017-09-01

    The study included 196 breast cancer patients with stages T1-3N0-3M0. The comprehensive therapy for breast cancer included surgical operation, chemotherapy, and radiotherapy. Multivariate analysis showed that multifocality growth of tumor (p = 0.004), high grade III (p = 0.008), two metastatic lymph nodes (p = 0.02) were associated with an increased risk of regional node failure in the patients with one to three positive lymph nodes. The prognostic models describing the probability of local recurrences of breast cancer were developed for individualization of the radiation therapy tactics. Postmastectomy radiation therapy in the patients with high-risk breast cancer treated with modified radical mastectomy improves locoregional control, breast cancer-specific survival, does not increase late toxicity.

  6. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Osuch, Czesław; Mierzejewska, Ewa; Wasielewski, Kacper; Woźniak, Agnieszka; Grzesiakowska, Urszula; Nowecki, Zbigniew I; Siedlecki, Janusz A; Limon, Janusz; Bylina, Elżbieta; Klimczak, Anna; Świtaj, Tomasz; Falkowski, Sławomir; Kroc, Jacek; Ługowska, Iwona; Brzeskwiniewicz, Magdalena; Melerowicz, Wojciech

    2012-01-01

    Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2 nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes. One year progression-free survival (PFS; calculated from the start of SU) rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM) was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks) in 55 patients with AH vs. 22% (median 17 weeks) in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively) than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively). We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism (OR: 10.0 p = 0.041 and OR: 10.5; p = 0

  7. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST after imatinib failure - one institution study

    Directory of Open Access Journals (Sweden)

    Rutkowski Piotr

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM or sunitinib (SU. Arterial hypertension (AH is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+ GIST patients after IM failure. Methods We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment. Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs of VEGFA and VEGFR2 genes. Results One year progression-free survival (PFS; calculated from the start of SU rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks in 55 patients with AH vs. 22% (median 17 weeks in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively. We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism

  8. Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

    Science.gov (United States)

    Lee, K H; Song, S U; Hwang, T S; Yi, Y; Oh, I S; Lee, J Y; Choi, K B; Choi, M S; Kim, S J

    2001-09-20

    Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

  9. Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

    Science.gov (United States)

    Park, Sehhoon; Park, Seongyeol; Lee, Se-Hoon; Suh, Beomseok; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Kim, Young Whan; Heo, Dae Seog

    2016-11-01

    Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

  10. The Play Factor: Effect of Social Skills Group Play Therapy on Adolescent African-American Males

    Science.gov (United States)

    Earls, Melissa K.

    2009-01-01

    The purpose of this study was to examine the effectiveness of Social Skills Group Play Therapy on remedying the social skills deficits of adolescent African-American males. Additionally, the study investigated whether age and grade level impacted the outcome of the intervention. The participants were adolescent African-American males ages 10 to…

  11. Therapist Factors in Internet-Delivered Cognitive Behavioural Therapy for Major Depressive Disorder

    NARCIS (Netherlands)

    Almlov, J.; Carlbring, P.; Berger, T.; Cuijpers, P.; Andersson, G.

    2009-01-01

    Internet-delivered cognitive behavioural therapy (CBT) can be an effective method for treating major depression, but it often works best when therapist support is provided in the form of e-mail support or telephone calls. The authors investigated whether there were any intraclass correlations within

  12. Factors affecting the choice of treatment in occupational therapy practices in hospital-based care.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1996-01-01

    The aim of this article was twofold: to describe the occurrence of treatment goals, health-care programmes and type of interventions chosen by occupational therapists; and to investigate relationships between treatment goals, health-care programmes and interventions. A survey on occupational therapy

  13. Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration

    International Nuclear Information System (INIS)

    Ding, Ying; Adachi, Hiroaki; Katsuno, Masahisa; Huang, Zhe; Jiang, Yue-Mei; Kondo, Naohide; Iida, Madoka; Tohnai, Genki; Nakatsuji, Hideaki; Funakoshi, Hiroshi; Nakamura, Toshikazu; Sobue, Gen

    2015-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within the androgen receptor (AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing an AR gene with an expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease-modifying therapies in SBMA. - Highlights: • HGF overexpression ameliorates the motor phenotypes of the SBMA mouse model. • HGF overexpression induces Akt phosphorylation in the SBMA mouse model. • This is the first report of combination therapy in a mouse model of polyQ diseases.

  14. Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ying [Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Adachi, Hiroaki, E-mail: hadachi-ns@umin.org [Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Department of Neurology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Katsuno, Masahisa [Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Huang, Zhe [Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Department of Neurology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Jiang, Yue-Mei; Kondo, Naohide; Iida, Madoka; Tohnai, Genki; Nakatsuji, Hideaki [Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Funakoshi, Hiroshi [Center for Advanced Research and Education, Asahikawa Medical University, 1-1-1- Higashinijo Midorigaoka, Asahikawa 078-8510 (Japan); Nakamura, Toshikazu [Neurogen Inc., 1-1-52-201 Nakahozumi, Ibaraki 567-0034 (Japan); Sobue, Gen, E-mail: sobueg@med.nagoya-u.ac.jp [Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2015-12-25

    Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within the androgen receptor (AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing an AR gene with an expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease-modifying therapies in SBMA. - Highlights: • HGF overexpression ameliorates the motor phenotypes of the SBMA mouse model. • HGF overexpression induces Akt phosphorylation in the SBMA mouse model. • This is the first report of combination therapy in a mouse model of polyQ diseases.

  15. Enhancing hair growth in male androgenetic alopecia by a combination of fractional CO2 laser therapy and hair growth factors.

    Science.gov (United States)

    Huang, Yue; Zhuo, Fenglin; Li, Linfeng

    2017-11-01

    Laser therapy and growth factors have been used as alternative treatments for male androgenetic alopecia (MAA). The aim of this study is to determine the efficacy and safety of hair growth factors alone or combined with ablative carbon dioxide (CO 2 ) fractional laser therapy in MAA. Twenty-eight men were enrolled in this randomized half-split study based on a left-head to right-head pattern. Fractional CO 2 laser treatment was unilaterally performed; hair growth factors were bilaterally applied. Six sessions with 2-week intervals were performed. Global photographs and dermoscopy assessments were performed at the baseline and 4 months after first treatment. Global photographs underwent blinded review by three independent dermatologists. Scanning electron microscopy was used to compare changes in hair-follicle phase and hair-shaft diameter. Twenty-seven participants completed the 4-month treatment schedule. One patient was lost. Mean hair density increased from 114 ± 27 to 143 ± 25/cm 2 (P laser combined with hair growth factors may serve as an alternative treatment for MAA in individuals unwilling/unable to undergo medical or surgical treatment.

  16. Geographic variation in long-term oxygen therapy in Denmark : factors related to adherence to guidelines for long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbæk, Thomas Jørgen; Lange, Peter; Viskum, K

    2001-01-01

    STUDY OBJECTIVES: To evaluate regional differences in adherence to guidelines for long-term oxygen therapy (LTOT) in Denmark and to determine factors related to compliance with these guidelines. DESIGN: Cross-sectional study and analysis of a nationwide database (Danish Oxygen Register). SETTING...... to national guidelines for LTOT was found in 34.4% of the patients for the whole of Denmark and varied regionally from 14 to 63%. Mean compliance with guidelines was 5.3 (range, 2.9 to 9.1) times as likely if the oxygen was prescribed by a pulmonary department compared to LTOT initiated by a GP. CONCLUSIONS......: Marked geographic variations in compliance with LTOT guidelines are present even in a small country as Denmark. In general, the adherence to the guidelines is poor, especially when non-chest physicians prescribe LTOT. We therefore recommend that local and national thoracic societies together with health...

  17. Influences of Pinpoint Plantar Long-Wavelength Infrared Light Irradiation (Stress-Free Therapy on Chorioretinal Hemodynamics, Atherosclerosis Factors, and Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Keisou Ishimaru

    2018-03-01

    Full Text Available Background: We previously reported that pinpoint plantar long-wavelength infrared light irradiation (stress-free therapy; SFT is useful for alleviating insulin resistance and improving intracranial blood flow in patients with type 2 diabetes mellitus. This study was undertaken to evaluate the influences of SFT on chorioretinal hemodynamics (retinal artery and vein blood flows as well as atherosclerosis-related factors (TG, LDL-C and VEGF in patients with dyslipidemia. Methods: Four patients with dyslipidemia received 15-minute irradiation with a stress-free apparatus (far-infrared wavelength, 30 mW. Using laser speckle flowgraphy, associations of chorioretinal blood flow with peripheral atherosclerosis-inducing factors/VEGF levels before and after irradiation were analyzed. Results: Chorioretinal blood flow increased, while TG/LDL-C levels decreased, after irradiation. VEGF tended to rise in cases with pre-irradiation baseline levels at the lower limit but tended to decrease in cases in which baseline levels had exceeded the normal range. Conclusion: SFT was suggested to enhance chorioretinal circulation and to normalize VEGF, thereby possibly contributing to amelioration of atherosclerosis-inducing factors. Abnormalities in chorioretinal hemodynamics are known to be highly involved in the pathophysiology of diabetic retinopathy and age-related macular degeneration, and anti-VEGF antibody has been used for treating these conditions. The necessity of risk management, involving chorioretinal blood flow, has been pointed out when dealing with central retinal vein occlusion, diabetes mellitus, ischemic cerebral/cardiac disease, dementia and so on. SFT is therefore a potential complementary medical strategy which can be expected to contribute to normalization of chorioretinal blood flow and atherosclerosis-inducing factors/VEGF levels, and thereby to the prevention of lifestyle-related chronic diseases. Keywords: Pinpoint plantar long

  18. Identifying patients with therapy-resistant depression by using factor analysis

    DEFF Research Database (Denmark)

    Andreasson, K; Liest, V; Lunde, M

    2010-01-01

    with transcranial pulsed electromagnetic fields (T-PEMF)], in which the relative effect as percentage of improvement during the treatment period was analysed. RESULTS: We identified 2 major factors, the first of which was a general factor. The second was a dual factor consisting of a depression subscale comprising...

  19. Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Michael G Liska

    2017-01-01

    Full Text Available Traumatic brain injury (TBI is now characterized as a progressive, degenerative disease and continues to stand as a prevalent cause of death and disability. The pathophysiology of TBI is complex, with a variety of secondary cell death pathways occurring which may persist chronically following the initial cerebral insult. Current therapeutic options for TBI are minimal, with surgical intervention or rehabilitation therapy existing as the only viable treatments. Considering the success of stem-cell therapies in various other neurological diseases, their use has been proposed as a potential potent therapy for patients suffering TBI. Moreover, stem cells are highly amenable to adjunctive use with other therapies, providing an opportunity to overcome the inherent limitations of using a single therapeutic agent. Our research has verified this additive potential by demonstrating the efficacy of co-delivering human umbilical cord blood (hUCB cells with granulocyte-colony stimulating factor (G-CSF in a murine model of TBI, providing encouraging results which support the potential of this approach to treat patients suffering from TBI. These findings justify ongoing research toward uncovering the mechanisms which underlie the functional improvements exhibited by hUCB + G-CSF combination therapy, thereby facilitating its safe and effect transition into the clinic. This paper is a review article. Referred literature in this paper has been listed in the reference section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  20. Affinity Purification of Tumor Necrosis Factor-α Expressed in Raji Cells by Produced scFv Antibody Coupled CNBr-Activated Sepharose

    Science.gov (United States)

    Abdolalizadeh, Jalal; Majidi Zolbanin, Jafar; Nouri, Mohammad; Baradaran, Behzad; Movassaghpour, AliAkbar; Farajnia, Safar; Omidi, Yadollah

    2013-01-01

    Purpose: Recombinant tumor necrosis factor-alpha (TNF-α) has been utilized as an antineoplastic agent for the treatment of patients with melanoma and sarcoma. It targets tumor cell antigens by impressing tumor-associated vessels. Protein purification with affinity chromatography has been widely used in the downstream processing of pharmaceutical-grade proteins. Methods:In this study, we examined the potential of our produced anti-TNF-α scFv fragments for purification of TNF-α produced by Raji cells. The Raji cells were induced by lipopolysaccharides (LPS) to express TNF-α. Western blotting and Fluorescence-activated cell sorting (FACS) flow cytometry analyses were used to evaluate the TNF-α expression. The anti-TNF-α scFv selected from antibody phage display library was coupled to CNBr-activated sepharose 4B beads used for affinity purification of expressed TNF-α and the purity of the protein was assessed by SDS-PAGE. Results: Western blot and FACS flow cytometry analyses showed the successful expression of TNF-α with Raji cells. SDS-PAGE analysis showed the performance of scFv for purification of TNF-α protein with purity over 95%. Conclusion: These findings confirm not only the potential of the produced scFv antibody fragments but also this highly pure recombinant TNF-α protein can be applied for various in vitro and in vivo applications. PMID:24312807

  1. Affinity Purification of Tumor Necrosis Factor-α Expressed in Raji Cells by Produced scFv Antibody Coupled CNBr-Activated Sepharose

    Directory of Open Access Journals (Sweden)

    Safar Farajnia

    2013-02-01

    Full Text Available Purpose: Recombinant tumor necrosis factor-alpha (TNF-α has been utilized as an antineoplastic agent for the treatment of patients with melanoma and sarcoma. It targets tumor cell antigens by impressing tumor-associated vessels. Protein purification with affinity chromatography has been widely used in the downstream processing of pharmaceutical-grade proteins. Methods: In this study, we examined the potential of our produced anti-TNF-scFv fragments for purification of TNF-α produced by Raji cells. he Raji cells were induced by lipopolysaccharides (LPS to express TNF-α. Western blotting and Fluorescence-activated cell sorting (FACS flow cytometry analyses were used to evaluate the TNF-α expression. The anti-TNF-α scFv selected from antibody phage display library was coupled to CNBr-activated sepharose 4B beads used for affinity purification of expressed TNF-α and the purity of the protein was assessed by SDS-PAGE. Results: Western blot and FACS flow cytometry analyses showed the successful expression of TNF-α with Raji cells. SDS-PAGE analysis showed the performance of scFv for purification of TNF-α protein with purity over 95%. Conclusion: These findings confirm not only the potential of the produced scFv antibody fragments but also this highly pure recombinant TNF-α protein can be applied for various in vitro and in vivo applications.

  2. Mediators of exposure therapy for youth obsessive-compulsive disorder: specificity and temporal sequence of client and treatment factors.

    Science.gov (United States)

    Chu, Brian C; Colognori, Daniela B; Yang, Guang; Xie, Min-ge; Lindsey Bergman, R; Piacentini, John

    2015-05-01

    Behavioral engagement and cognitive coping have been hypothesized to mediate effectiveness of exposure-based therapies. Identifying which specific child factors mediate successful therapy and which therapist factors facilitate change can help make our evidence-based treatments more efficient and robust. The current study examines the specificity and temporal sequence of relations among hypothesized client and therapist mediators in exposure therapy for pediatric Obsessive Compulsive Disorder (OCD). Youth coping (cognitive, behavioral), youth safety behaviors (avoidance, escape, compulsive behaviors), therapist interventions (cognitive, exposure extensiveness), and youth anxiety were rated via observational ratings of therapy sessions of OCD youth (N=43; ages=8 - 17; 62.8% male) who had received Exposure and Response Prevention (ERP). Regression analysis using Generalized Estimation Equations and cross-lagged panel analysis (CLPA) were conducted to model anxiety change within and across sessions, to determine formal mediators of anxiety change, and to establish sequence of effects. Anxiety ratings decreased linearly across exposures within sessions. Youth coping and therapist interventions significantly mediated anxiety change across exposures, and youth-interfering behavior mediated anxiety change at the trend level. In CLPA, youth-interfering behaviors predicted, and were predicted by, changes in anxiety. Youth coping was predicted by prior anxiety change. The study provides a preliminary examination of specificity and temporal sequence among child and therapist behaviors in predicting youth anxiety. Results suggest that therapists should educate clients in the natural rebound effects of anxiety between sessions and should be aware of the negatively reinforcing properties of avoidance during exposure. Copyright © 2015. Published by Elsevier Ltd.

  3. How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.

    Science.gov (United States)

    Hammerstingl, Christoph; Omran, Heyder; Tripp, Christian; Poetzsch, Bernd

    2009-02-01

    Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 +/- 10.8 years, Cr Cl 55.7 +/- 21.7ml/min, body mass index [BMI] 27.1 +/- 4.9). LMWH- therapy was for a mean of 4.2 +/- 1.6 days; overall anti-Xa was 0.58 +/- 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was > or U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.

  4. Increased Bowel Toxicity in Patients Treated With a Vascular Endothelial Growth Factor Inhibitor (VEGFI) After Stereotactic Body Radiation Therapy (SBRT)

    Energy Technology Data Exchange (ETDEWEB)

    Barney, Brandon M., E-mail: barney.brandon@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Markovic, Svetomir N. [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Laack, Nadia N.; Miller, Robert C.; Sarkaria, Jann N. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Macdonald, O. Kenneth [Therapeutic Radiologists Incorporated, Kansas City, Kansas (United States); Bauer, Heather J.; Olivier, Kenneth R. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2013-09-01

    Purpose: Gastrointestinal injury occurs rarely with agents that affect the vascular endothelial growth factor receptor and with abdominal stereotactic body radiation therapy (SBRT). We explored the incidence of serious bowel injury (SBI) in patients treated with SBRT with or without vascular endothelial growth factor inhibitor (VEGFI) therapy. Methods and Materials: Seventy-six patients with 84 primary or metastatic intra-abdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Of the patients, 20 (26%) received VEGFI within 2 years after SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The incidence of SBI (Common Terminology Criteria for Adverse Events, version 4.0, grade 3-5 ulceration or perforation) after SBRT was obtained, and the relationship between SBI and VEGFI was examined. Results: In the combined population, 7 patients (9%) had SBI at a median of 4.6 months (range, 3-17 months) from SBRT. All 7 had received VEGFI before SBI and within 13 months of completing SBRT, and 5 received VEGFI within 3 months of SBRT. The 6-month estimate of SBI in the 26 patients receiving VEGFI within 3 months of SBRT was 38%. No SBIs were noted in the 63 patients not receiving VEGFI. The log–rank test showed a sig