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Publisher: Springer-Verlag (Total: 2350 journals)

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Showing 1 - 200 of 2350 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 1)
3D Research     Hybrid Journal   (Followers: 21, SJR: 0.222, CiteScore: 1)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.825, CiteScore: 1)
AAPS J.     Hybrid Journal   (Followers: 22, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.752, CiteScore: 3)
Abdominal Imaging     Hybrid Journal   (Followers: 15, SJR: 0.866, CiteScore: 2)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 4, SJR: 0.439, CiteScore: 0)
Academic Psychiatry     Full-text available via subscription   (Followers: 25, SJR: 0.53, CiteScore: 1)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.106, CiteScore: 0)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 27, SJR: 0.316, CiteScore: 1)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.359, CiteScore: 1)
Acoustics Australia     Hybrid Journal   (SJR: 0.232, CiteScore: 1)
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.367, CiteScore: 0)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.675, CiteScore: 1)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.284, CiteScore: 1)
Acta Diabetologica     Hybrid Journal   (Followers: 18, SJR: 1.587, CiteScore: 3)
Acta Endoscopica     Hybrid Journal   (Followers: 1)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.769, CiteScore: 1)
Acta Geochimica     Hybrid Journal   (Followers: 7, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.305, CiteScore: 1)
Acta Geophysica     Hybrid Journal   (Followers: 10, SJR: 0.312, CiteScore: 1)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.588, CiteScore: 3)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.517, CiteScore: 1)
Acta Mathematica     Hybrid Journal   (Followers: 12, SJR: 7.066, CiteScore: 3)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.452, CiteScore: 1)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.379, CiteScore: 1)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.27, CiteScore: 0)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.208, CiteScore: 0)
Acta Mechanica     Hybrid Journal   (Followers: 21, SJR: 1.04, CiteScore: 2)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.607, CiteScore: 2)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7, SJR: 0.576, CiteScore: 2)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.638, CiteScore: 1)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.822, CiteScore: 2)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 1, SJR: 0.376, CiteScore: 1)
Acta Neuropathologica     Hybrid Journal   (Followers: 5, SJR: 7.589, CiteScore: 12)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.334, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 15, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8, SJR: 0.103, CiteScore: 0)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 23, SJR: 0.72, CiteScore: 2)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 16, SJR: 1.005, CiteScore: 2)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.703, CiteScore: 2)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.698, CiteScore: 1)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 37, SJR: 0.956, CiteScore: 2)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 19, SJR: 0.812, CiteScore: 1)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 54, SJR: 1.09, CiteScore: 1)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.144, CiteScore: 0)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 28, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 44, SJR: 1.04, CiteScore: 3)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 1.075, CiteScore: 3)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 6)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.517, CiteScore: 1)
Aerobiologia     Hybrid Journal   (Followers: 3, SJR: 0.673, CiteScore: 2)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 9, SJR: 0.825, CiteScore: 1)
African Archaeological Review     Hybrid Journal   (Followers: 16, SJR: 0.862, CiteScore: 1)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.235, CiteScore: 0)
AGE     Hybrid Journal   (Followers: 7)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.39, CiteScore: 1)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.67, CiteScore: 2)
Agricultural Research     Hybrid Journal   (Followers: 6, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Hybrid Journal   (Followers: 20, SJR: 0.663, CiteScore: 1)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 12, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 8, SJR: 0.227, CiteScore: 1)
AIDS and Behavior     Hybrid Journal   (Followers: 14, SJR: 1.792, CiteScore: 3)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.862, CiteScore: 3)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 6, SJR: 0.531, CiteScore: 0)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.583, CiteScore: 1)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 1.095, CiteScore: 1)
Algorithmica     Hybrid Journal   (Followers: 9, SJR: 0.56, CiteScore: 1)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.234, CiteScore: 0)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 1.11, CiteScore: 3)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
AMBIO     Hybrid Journal   (Followers: 10, SJR: 1.569, CiteScore: 4)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.951, CiteScore: 3)
American J. of Community Psychology     Hybrid Journal   (Followers: 29, SJR: 1.329, CiteScore: 2)
American J. of Criminal Justice     Hybrid Journal   (Followers: 8, SJR: 0.772, CiteScore: 1)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 16, SJR: 0.46, CiteScore: 1)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.181, CiteScore: 0)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.611, CiteScore: 1)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 21, SJR: 0.314, CiteScore: 0)
American Sociologist     Hybrid Journal   (Followers: 12, SJR: 0.35, CiteScore: 0)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.135, CiteScore: 3)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.211, CiteScore: 1)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 5, SJR: 0.536, CiteScore: 1)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 5)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 0.978, CiteScore: 3)
Anatomical Science Intl.     Hybrid Journal   (Followers: 2, SJR: 0.367, CiteScore: 1)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.177, CiteScore: 5)
Animal Cognition     Hybrid Journal   (Followers: 19, SJR: 1.389, CiteScore: 3)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.192, CiteScore: 0)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.097, CiteScore: 2)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4, SJR: 0.438, CiteScore: 0)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.429, CiteScore: 0)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.197, CiteScore: 1)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.042, CiteScore: 3)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.932, CiteScore: 1)
Annals of Data Science     Hybrid Journal   (Followers: 12)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.85, CiteScore: 2)
Annals of Finance     Hybrid Journal   (Followers: 30, SJR: 0.579, CiteScore: 1)
Annals of Forest Science     Hybrid Journal   (Followers: 7, SJR: 0.986, CiteScore: 2)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.228, CiteScore: 1)
Annals of Hematology     Hybrid Journal   (Followers: 15, SJR: 1.043, CiteScore: 2)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.413, CiteScore: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 11, SJR: 0.479, CiteScore: 2)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4, SJR: 0.687, CiteScore: 2)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 11)
Annals of Regional Science     Hybrid Journal   (Followers: 7, SJR: 0.614, CiteScore: 1)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 9, SJR: 0.239, CiteScore: 1)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 13, SJR: 1.986, CiteScore: 4)
Annals of Telecommunications     Hybrid Journal   (Followers: 9, SJR: 0.223, CiteScore: 1)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 1.495, CiteScore: 1)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.834, CiteScore: 2)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.22, CiteScore: 3)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.424, CiteScore: 4)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.294, CiteScore: 1)
Applications of Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.602, CiteScore: 1)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 43, SJR: 0.571, CiteScore: 2)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17, SJR: 0.21, CiteScore: 1)
Applied Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 49, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 4, SJR: 0.422, CiteScore: 1)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.733, CiteScore: 3)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.488, CiteScore: 1)
Applied Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 6, SJR: 0.886, CiteScore: 1)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.17, CiteScore: 0)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.461, CiteScore: 1)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 64, SJR: 1.182, CiteScore: 4)
Applied Physics A     Hybrid Journal   (Followers: 9, SJR: 0.481, CiteScore: 2)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 24, SJR: 0.74, CiteScore: 2)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.519, CiteScore: 2)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 12, SJR: 0.316, CiteScore: 1)
Applied Solar Energy     Hybrid Journal   (Followers: 18, SJR: 0.225, CiteScore: 0)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 5, SJR: 0.542, CiteScore: 1)
Aquaculture Intl.     Hybrid Journal   (Followers: 24, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 2)
Aquatic Ecology     Hybrid Journal   (Followers: 34, SJR: 0.656, CiteScore: 2)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.591, CiteScore: 1)
Aquatic Sciences     Hybrid Journal   (Followers: 13, SJR: 1.109, CiteScore: 3)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.303, CiteScore: 1)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 2, SJR: 0.319, CiteScore: 1)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 20, SJR: 1.052, CiteScore: 2)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.224, CiteScore: 0)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.725, CiteScore: 1)
Archival Science     Hybrid Journal   (Followers: 60, SJR: 0.745, CiteScore: 2)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 3, SJR: 0.909, CiteScore: 1)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 3.93, CiteScore: 3)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Archives and Museum Informatics     Hybrid Journal   (Followers: 144, SJR: 0.101, CiteScore: 0)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 5, SJR: 1.41, CiteScore: 5)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 1.006, CiteScore: 2)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 14, SJR: 0.773, CiteScore: 2)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 16, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.644, CiteScore: 2)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.146, CiteScore: 2)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 0.71, CiteScore: 2)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.493, CiteScore: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.541, CiteScore: 5)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 0.973, CiteScore: 2)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 14, SJR: 1.274, CiteScore: 3)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 0.946, CiteScore: 3)
ArgoSpine News & J.     Hybrid Journal  
Argumentation     Hybrid Journal   (Followers: 6, SJR: 0.349, CiteScore: 1)
Arid Ecosystems     Hybrid Journal   (Followers: 2, SJR: 0.2, CiteScore: 0)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.766, CiteScore: 1)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1, SJR: 0.355, CiteScore: 0)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.839, CiteScore: 2)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.131, CiteScore: 0)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.937, CiteScore: 2)
Artificial Intelligence Review     Hybrid Journal   (Followers: 15, SJR: 0.833, CiteScore: 4)
Artificial Life and Robotics     Hybrid Journal   (Followers: 9, SJR: 0.226, CiteScore: 0)
Asia Europe J.     Hybrid Journal   (Followers: 5, SJR: 0.504, CiteScore: 1)
Asia Pacific Education Review     Hybrid Journal   (Followers: 12, SJR: 0.479, CiteScore: 1)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.185, CiteScore: 2)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 12, SJR: 0.353, CiteScore: 1)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.187, CiteScore: 0)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 19, SJR: 0.855, CiteScore: 1)
Asian Business & Management     Hybrid Journal   (Followers: 9, SJR: 0.378, CiteScore: 1)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 9)
Asian J. of Criminology     Hybrid Journal   (Followers: 6, SJR: 0.543, CiteScore: 1)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 3, SJR: 0.548, CiteScore: 1)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.183, CiteScore: 0)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  

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Journal Cover
Advances in Therapy
Journal Prestige (SJR): 1.075
Citation Impact (citeScore): 3
Number of Followers: 5  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1865-8652 - ISSN (Online) 0741-238X
Published by Springer-Verlag Homepage  [2350 journals]
  • Calgranulin A (S100A8) Immunostaining: A Future Candidate for Risk
           Assessment in Patients with Non-Muscle-Invasive Bladder Cancer (NMIBC)
    • Abstract: Introduction There is an urgent need to identify patients with bladder cancer (BC) who are at high risk of recurrence or progression. Calgranulin A is a strong marker for muscle-invasive or advanced BC and recent studies have shown its potential for identifying patients at risk even in non-muscle-invasive bladder cancer (NMIBC). The present study examines risks of recurrence and progression dependent on immunostaining with calgranulin A in NMIBC. Methods Calgranulin A protein expression was evaluated through the immunohistochemistry of 158 randomly selected, transurethrally resected BC specimens of separate patients (pTa 89, pT1 69) using tissue microarrays. Kaplan–Meier survival analysis and Cox regression were performed to determine whether calgranulin A expression is associated with recurrence-free survival (RFS), progression-free survival (PFS), or cancer-specific survival (CSS). Results Calgranulin A expression is significantly different between pTa and pT1 tumors (p = 0.000, Mann–Whitney U test) and between tumor grades (p = 0.015, Kruskal–Wallis test). Kaplan–Meier estimates produced significant results for low and high calgranulin A expression concerning RFS [5y-RFS 70.4 ± 4.0% vs. 35.9 ± 12.5%, median RFS not reached (NR) vs. 12.0 ± 4.4 month, p = 0.029, log-rank test], PFS (5y-PFS 90.3 ± 2.7% vs. 51.5 ± 14.0%, median PFS NR in both groups, p = 0.000, log-rank test), and CSS (5y-CSS 92.9 ± 2.6% vs. 70.7 ± 12.4%, median CSS NR in both groups, p = 0.005, log-rank test). Calgranulin A remained an independent factor for RFS (p = 0.024, HR 2.43) and PFS (p = 0.002, HR 5.92) according to the multivariate Cox regression model. Conclusions Calgranulin A expression in NMIBC, detected through immunohistochemistry, is a promising marker for the identification of NMIBC patients at high risk of recurrence and progression.
      PubDate: 2018-09-19
  • Patient Diversity and Population Health-Related Cardiovascular Outcomes
           Associated with Warfarin Use in Atrial Fibrillation: An Analysis Using
           Administrative Claims Data
    • Abstract: Introduction Anticoagulants are effective for stroke prevention in atrial fibrillation (AF). Data on population health-related cardiovascular outcomes by race/ethnicity and gender are not well described. The aim was to assess the impact of patient diversity on associated cardiovascular outcomes related to warfarin anticoagulation in Medicare beneficiaries with AF. Methods Medicare administrative claims data for years 2000–2010 were used to calculate AF prevalence and rates of new AF cases. Three 20% sample cohorts of new AF beneficiaries for years 2000, 2005, and 2007 were extracted and analyzed in a longitudinal study design. The impact of warfarin on associated cardiovascular outcomes was measured with respect to race/ethnicity and gender. Measured outcomes included the risk of stroke, mortality and hospitalization after adjusting for age, gender, race/ethnicity, CHADS2 score and warfarin. Results AF prevalence and warfarin use increased while stroke and mortality rates declined across race/ethnicity and gender from 2000 to 2010. Analyses comparing Whites to non-Whites highlighted several disparities: (1) Blacks were 40% (p < 0.0001) more likely to have a stroke even after adjustment for warfarin; (2) in 2007, Hispanics had a 35% (p < 0.01) higher prevalence of stroke and warfarin did not reduce the risk; and (3) Asians had better outcomes. Warfarin reduced stroke less well in women who had a lower risk of death and hospitalization. Despite a > 70% (p < 0.0001) reduction in mortality for warfarin users, Blacks had a 25% (p < 0.0001) higher mortality risk than Whites. Conclusions Differences in population health metrics across race/ethnicity and gender exist in AF. Across all metrics, Blacks had comparatively worse outcomes. Patient diversity should be a focus for future investigations in AF to improve outcomes in the whole population. Funding National Minority Quality Forum.
      PubDate: 2018-09-15
      DOI: 10.1007/s12325-018-0782-1
  • An Update of Efficacy and Safety of Cetuximab in Metastatic Colorectal
           Cancer: A Narrative Review
    • Authors: Giulia Fornasier; Sara Francescon; Paolo Baldo
      Abstract: Abstract Colorectal cancer is the second most common cancer, representing 13% of all diagnosed cancers. Cetuximab is a recombinant chimeric monoclonal IgG1 antibody and epidermal growth factor receptor (EGFR) inhibitor. Cetuximab is approved for the first-line treatment in combination with chemotherapy or as a single agent in patients who have failed or are intolerant to chemotherapy in patients with EGFR-expressing, RAS wild-type metastatic colorectal cancer. Cetuximab efficacy emerged from studies that were conducted to approve the drug. Cetuximab is well tolerated; its toxicities are caused by its mechanism of action and the most common adverse reaction is skin toxicity. The main purpose of this manuscript is to present an update on the evidence-based summary of efficacy and safety and on the cost-effectiveness of cetuximab. Furthermore, it suggests a management of adverse drug reactions to improve the tolerability of the drug.
      PubDate: 2018-09-14
      DOI: 10.1007/s12325-018-0791-0
  • Correction to: Expected Budget Impact and Health Outcomes of Expanded Use
           of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy
    • Authors: Molly F. Purser; Deirdre M. Mladsi; Alan Beckman; Francesca Barion; John Forsey
      Abstract: The article “Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy”, written by Molly F. Purser, Deirdre M. Mladsi, Alan Beckman, Francesca Barion, John Forsey was originally published electronically on the publisher’s internet portal (currently SpringerLink) on August 24, 2018 without open access.
      PubDate: 2018-09-12
      DOI: 10.1007/s12325-018-0787-9
  • Diagnostic Accuracy of Bronchodilator Response for Asthma in a Population
           of South China
    • Authors: Shichuan Zhang; Chengping Hu; Rongli Lu; Ruichao Niu; Xinyue Hu; Ling Qin; Ruoxi He; Juntao Feng
      Abstract: Introduction A significant bronchodilator response is commonly defined as a 12% or greater and 200 ml or greater change in FEV1 from baseline according to the 2005 American Thoracic Society (ATS)/European Respiratory Society (ERS) criterion. A number of studies have shown that the ATS/ERS criterion has limitations in asthma diagnosis, and some experts have argued for correcting the criteria. The aim of this study is to investigate the diagnostic value of acute bronchodilator response for asthma in a Southern Chinese population. Methods We prospectively evaluated 805 patients with obstructive lung disease (309 for asthma, 496 for non-asthma). Spirometry was performed according to the ATS/ERS guidelines. Data were analyzed by SPSS 18.0. The receiver-operating characteristic (ROC) curve was drawn to assess the diagnostic accuracy of the ATS/ERS criterion based on FEV1. Linear regression was used to analyze the factors of FEV1 change. Results The sensitivity and specificity of the acute bronchodilator test when judged by the ATS/ERS criteria (200 ml or higher and 12% improvement) were 68.6% and 78.2%, respectively. For the ATS/ERS criteria, the Youden Index, which comprehensively reflects the authenticity of a diagnostic test, was 46.8%. The absolute change of FEV1 positively correlated with baseline FEV1 and weight and negatively with age, while the percentage change of FEV1 was negatively correlated with baseline FEV1, age and height and positively with weight. Compared with the different diagnostic values, when ∆FEV1 was 195 ml and ∆FEV1i% was 14%, the Youden Index was the largest (48.2%) and the diagnostic capability of the test the biggest. Conclusions The ATS/ERS criterion for acute bronchodilator response might not be completely suitable for asthma in the Chinese population. Trial Registration Chinese Clinical Trial Registry (Registry ID: ChiCTR-DDT-14004976). Funding This work was supported by the National Natural Science Foundation of China (grant nos. 81670027, 81270080).
      PubDate: 2018-09-12
      DOI: 10.1007/s12325-018-0783-0
  • Comparative Effectiveness of nab -Paclitaxel Plus Gemcitabine vs
           FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide
           Chart Review in the United States
    • Authors: Sunnie Kim; James E. Signorovitch; Hongbo Yang; Oscar Patterson-Lomba; Cheryl Q. Xiang; Brian Ung; Monika Parisi; John L. Marshall
      Abstract: Introduction nab-Paclitaxel plus gemcitabine (nab-P + G) and FOLFIRINOX (FFX) are among the most common first-line (1L) therapies for metastatic adenocarcinoma of the pancreas (MPAC), but real-world data on their comparative effectiveness are limited. Methods This retrospective cohort study compared the efficacy and safety of 1L nab-P + G versus FFX, overall and under specific treatment sequences. Medical records were reviewed by 215 US physicians who provided information on MPAC patients who initiated 1L therapy with nab-P + G or FFX between April 1, 2015 and December 31, 2015. Study outcomes were overall survival (OS) and tolerability. OS was compared using Kaplan–Meier curves and adjusted Cox proportional hazards models. Results In total, 654 medical records were reviewed, including those of 337 and 317 patients initiated on nab-P + G and FFX as 1L MPAC therapy, respectively. nab-P + G-initiated patients were older, less likely to have ECOG ≤ 1, and had more comorbidities than FFX-initiated patients. Median OS (mOS) was 12.1 and 13.8 months for nab-P + G- and FFX-initiated patients, respectively (HR = 0.99, P = 0.96). Among patients with ECOG ≤ 1, mOS was 14.1 and 13.7 months, respectively (HR = 1.00, P = 0.99). Among patients with 1L nab-P + G and FFX, 36.1% and 41.3% received 2L therapy and experienced mOS of 16.3 and 16.6 months, respectively (HR = 1.04, P = 0.76). The rates of diarrhea, fatigue, mucositis, and nausea and vomiting were significantly higher in the FFX than nab-P + G cohort. Conclusion The real-world survival was similar between patients receiving 1L nab-P + G or FFX both overall and among patients who received active 2L treatments. In addition, nab-P + G was associated with significantly lower rates of common AEs compared with FFX. Funding Celgene.
      PubDate: 2018-09-12
      DOI: 10.1007/s12325-018-0784-z
  • 72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients
           with Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised,
           Double Blind, Placebo-Controlled, Phase III APEX Study and its Open-Label
    • Authors: Hirofumi Ochi; Masaaki Niino; Yasuhiro Onizuka; Katsutoshi Hiramatsu; Masakazu Hase; Jang Yun; André Matta; Shinichi Torii
      Abstract: Introduction The long-term safety of dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (RRMS) has been studied in mainly Caucasian patients. The present interim analysis aimed to evaluate the 72-week safety of DMF in Japanese patients with RRMS. Methods Safety data of Japanese subjects enrolled in the 24-week randomised, double-blind, placebo-controlled APEX study (Part I) and its following open-label extension (Part II) were analysed at 72 weeks from the beginning of Part I. In Part I, subjects were randomised to DMF treatment or matching placebo while all subjects received DMF treatment during Part II. Adverse events (AEs) reported throughout the study period were recorded. Results Overall, 109 Japanese subjects completed 72 weeks of treatment. The incidence of AEs and serious AEs was 95% and 19%, respectively, in the DMF group compared with 84% and 18%, respectively, in the placebo group at 24 weeks. Common AEs (at least 5%) reported with treatment included nasopharyngitis, flushing, hot flush, gastrointestinal events, pruritus, rash, headache, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). AEs led to discontinuation of DMF in 5% of patients and included MS relapse, flushing, abdominal pain, liver disorder and increased ALT/AST. After an initial decrease from baseline of 17% in the DMF group at week 24, the mean lymphocyte counts stabilised and were maintained until week 72. No opportunistic/serious infections nor malignancies were reported with DMF treatment. The incidences of AEs, serious AEs, and discontinuation due to AEs were similar between the DMF and the placebo groups. Conclusion The 72-week safety profile of DMF in Japanese patients with RRMS was consistent with previous studies that enrolled mostly Caucasian patients, with a lower incidence of flushing and related symptoms and a lower reduction in the lymphocyte count compared with previous reports. Trial Registration identifier NCT01838668. Funding Biogen Japan Ltd.
      PubDate: 2018-09-11
      DOI: 10.1007/s12325-018-0788-8
  • Does ‘Strong Analgesic’ Equal ‘Strong Opioid’' Tapentadol and
           the Concept of ‘µ-Load’
    • Authors: Robert B. Raffa; Christian Elling; Thomas M. Tzschentke
      Abstract: Introduction The distinct properties of the centrally-acting analgesic tapentadol derive from the combined contributions of an opioid component and a nonopioid component. However, the opioid component’s relative contribution to analgesic and adverse effects has not previously been elucidated. Tapentadol’s analgesic effect derives from the combined contribution of an opioid mechanism and a nonopioid mechanism, the extent of which can vary for different pains. Likewise, the interaction can vary for various adverse effects. Hence, the contribution of each mechanism to adverse effects can be different from the contribution to analgesia. We here estimate the percent contribution of each component of the mechanism of action to analgesia and to adverse effects. Areas Covered Several approaches to in vitro and in vivo data to estimate the contribution of tapentadol’s opioid component to analgesia and to the two important opioid adverse effects, respiratory depression and constipation. The results are then compared with clinical data. Expert Opinion Traditional opioids, such as morphine, oxycodone, and others, produce their analgesic effects primarily through a single mechanism—the activation of µ-opioid receptors (MOR). Therefore, the contribution of the opioid component to adverse effects is 100%. In contrast, the newer strong analgesic tapentadol produces its analgesic effect via two separate and complementary analgesic mechanisms, only one of which is µ-opioid. We applied standard drug–receptor theory and novel techniques to in vitro and in vivo data to estimate by several different ways the μ-load of tapentadol (the % contribution of the opioid component to the adverse effect magnitude relative to a pure/classical µ-opioid at equianalgesia) in respiratory depression and constipation, and we compared the results to clinical evidence. The estimate is remarkably consistent over the various approaches and indicates that the μ-load of tapentadol is ≤ 40% (relative to pure MOR agonists, which have, by definition, a µ-load of 100%). Funding Grünenthal GmbH.
      PubDate: 2018-09-11
      DOI: 10.1007/s12325-018-0778-x
  • Predicting Responses to Pregabalin for Painful Diabetic Peripheral
           Neuropathy Based on Trajectory-Focused Patient Profiles Derived from the
           First 4 Weeks of Treatment
    • Authors: Roger A. Edwards; Gianluca Bonfanti; Roberto Grugni; Luigi Manca; Bruce Parsons; Joe Alexander
      Abstract: Introduction Prediction of final clinical outcomes based on early weeks of treatment can enable more effective patient care for chronic pain. Our goal was to predict, with at least 90% accuracy, 12- to 13-week outcomes for pregabalin-treated painful diabetic peripheral neuropathy (pDPN) patients based on 4 weeks of pain and pain-related sleep interference data. Methods We utilized active treatment data from six placebo-controlled randomized controlled trials (n = 939) designed to evaluate efficacy of pregabalin for reducing pain in patients with pDPN. We implemented a three-step, trajectory-focused analytics approach based upon patient responses collected during the first 4 weeks using monotonicity, path length, frequency domain (FD), and k-nearest neighbor (kNN) methods. The first two steps were based on combinations of baseline pain, pain at 4 weeks, weekly monotonicity and path length during the first 4 weeks, and assignment of patients to one of four responder groups (based on presence/absence of 50% or 30% reduction from baseline pain at 4 and at 12/13 weeks). The third step included agreement between prediction of logistic regression of daily FD amplitudes and assignment made from kNN analyses. Results Step 1 correctly assigned 520/939 patients from the six studies to a responder group using a 3-metric combination approach based on unique assignment to a 50% responder group. Step 2 (applied to the remaining 419 patients) predicted an additional 121 patients, using a blend of 50% and 30% responder thresholds. Step 3 (using a combination of FD and kNN analyses) predicted 204 of the remaining 298 patients using the 50% responder threshold. Our approach correctly predicted 90.0% of all patients. Conclusion By correctly predicting 12- to 13-week responder outcomes with 90% accuracy based on responses from the first month of treatment, we demonstrated the value of trajectory measures in predicting pDPN patient response to pregabalin. Trial Registration identifiers, NCT00156078/NCT00159679/NCT00143156/NCT00553475. Funding Pfizer. Plain Language Summary Plain language summary available for this article.
      PubDate: 2018-09-11
      DOI: 10.1007/s12325-018-0780-3
  • Medication Adherence and Discontinuation of Aripiprazole Once-Monthly
           400 mg (AOM 400) Versus Oral Antipsychotics in Patients with
           Schizophrenia or Bipolar I Disorder: A Real-World Study Using US Claims
    • Authors: Tingjian Yan; Mallik Greene; Eunice Chang; Ann Hartry; Maëlys Touya; Michael S. Broder
      Abstract: Introduction Few studies have compared adherence between long-acting injectable antipsychotics, especially for newer agents like aripiprazole once-monthly 400 mg (AOM 400; aripiprazole monohydrate) and oral antipsychotics, in patients with schizophrenia or bipolar I disorder (BD-I) in a real-world setting. Methods Two separate retrospective cohort analyses using Truven MarketScan data from January 1, 2012 to June 30, 2016 were conducted to compare medication adherence and discontinuation in patients with schizophrenia or BD-I who initiated treatment with AOM 400 vs. patients changed from one oral antipsychotic monotherapy to another. Adherence was defined as proportion of days covered (PDC) ≥ 0.80 in the year following the index date. Linear regression models examined the association between AOM 400 and oral antipsychotic cohorts and medication adherence. Kaplan–Meier curves and Cox regression estimated time to and risk of discontinuation, while adjusting for baseline covariates. A sensitivity analysis was conducted using a combination of propensity score matching and exact matching to create matched cohorts. Results Final cohort sizes were as follows—Schizophrenia: AOM 400 n = 408, oral antipsychotic n = 3361; BD-I: AOM 400 n = 413, oral antipsychotic n = 15,534. In patients with schizophrenia, adjusted mean PDC was higher in patients in the AOM 400 cohort vs. the oral antipsychotic cohort (0.57 vs. 0.48 P < 0.001), and patients in the oral antipsychotic cohort had a higher risk of discontinuing treatment vs. the AOM 400 cohort (HR 1.45, 95% CI 1.29–1.64). For patients with BD-I, adjusted mean PDC was higher for the AOM 400 cohort (0.59 vs. 0.44, P < 0.001), and patients in the oral antipsychotic cohort had a higher risk of discontinuation (HR 1.71, 95% CI 1.53–1.92). Conclusions In a real-word setting, AOM 400 resulted in a significantly higher percentage of patients with a PDC ≥ 0.80 and significantly longer time to treatment discontinuation compared to patients with schizophrenia or BD-I who received treatment with an oral antipsychotic. Funding Otsuka Pharmaceutical Development and Commercialization, Inc. and Lundbeck.
      PubDate: 2018-09-11
      DOI: 10.1007/s12325-018-0785-y
  • Real-world Management of Women with Postmenopausal Osteoporosis Treated
           with Denosumab: A Prospective Observational Study in the Czech Republic
           and Slovakia
    • Authors: Olga Růžičková; Zdenko Killinger; Petr Kasalický; Lisa Hamilton; Roman Tyl; Soňa Tomková; Lama Kalouche-Khalil
      Abstract: Introduction Osteoporosis is characterized by low bone mineral density (BMD) and an increased risk of fracture. In randomized controlled trials, denosumab has been shown to significantly reduce the fracture risk in women with osteoporosis. However, little is known about the real-world management of women who are prescribed denosumab. Methods This multicenter, prospective, observational real-world study in the Czech Republic and Slovakia evaluated the baseline characteristics and clinical management of women with postmenopausal osteoporosis prescribed denosumab for 24 months. Results A total of 600 women were included (300 in each country). In the Czech Republic and Slovakia, respectively, mean age at enrollment was 69.0 and 64.3 years, 67.7% and 30.0% of patients had a previous osteoporotic fracture, and 85.0% and 48.7% had previously received osteoporosis medication. In both countries, ‘low BMD T score’ and ‘a history of osteoporotic fracture’ were the main reasons for prescribing denosumab. Most patients received all four post-baseline denosumab injections (Czech Republic, 82.0%; Slovakia, 81.0%), and more than 98% of patients in both countries received all injections at the prescribing center. At 24 months, most patients experienced an increase in BMD T score for the lumbar spine, total hip, or femoral neck (Czech Republic, 69.7–91.7%; Slovakia, 67.1–92.9%). Adverse drug reactions were consistent with the known safety profile of denosumab. Conclusion Baseline characteristics of patients receiving denosumab in the Czech Republic and Slovakia reflect the reimbursement criteria for this agent in each country. The findings of our study in patients who are at high risk for fracture are consistent with the growing body of evidence demonstrating the effectiveness of denosumab in real-world clinical practice. Trial Registration identifier, NCT01652690. Funding Amgen Inc.
      PubDate: 2018-09-06
      DOI: 10.1007/s12325-018-0779-9
  • Preventing Clinically Important Deterioration of COPD with Addition of
           Umeclidinium to Inhaled Corticosteroid/Long-Acting β 2 -Agonist Therapy:
           An Integrated Post Hoc Analysis
    • Authors: Ian P. Naya; Lee Tombs; David A. Lipson; Chris Compton
      Abstract: Introduction Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD). This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone. Methods This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2). A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation. Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy. Adverse events (AEs) were also assessed. Results Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818). Additional bronchodilation with UMEC reduced the risk of a first CID by 45–58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001). Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population. No significant reduction in risk of a SGRQ CID was observed. AE incidence was similar between treatment groups. Conclusion Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations. Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients. Funding GlaxoSmithKline (study number: 202067). Plain Language Summary Plain language summary available for this article.
      PubDate: 2018-09-06
      DOI: 10.1007/s12325-018-0771-4
  • Treatment Duration, Healthcare Resource Utilization, and Costs Among
           Chemotherapy-Naïve Patients with Metastatic Castration-Resistant Prostate
           Cancer Treated with Enzalutamide or Abiraterone Acetate: A Retrospective
           Claims Analysis
    • Authors: Neil M. Schultz; Scott C. Flanders; Samuel Wilson; Bruce A. Brown; Yan Song; Hongbo Yang; Stanislav Lechpammer; Vahan Kassabian
      Abstract: Introduction Enzalutamide and abiraterone acetate (plus prednisone) are new hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC). This study compared treatment duration, healthcare resource utilization (HRU), and treatment costs for chemotherapy-naïve mCRPC patients treated with enzalutamide or abiraterone acetate in the USA. Methods Chemotherapy-naïve mCRPC patients initiating treatment with enzalutamide or abiraterone acetate were identified from administrative claims. Continuous enrollment ≥ 6 months before and ≥ 3 months after the index date (initiation date of enzalutamide or abiraterone acetate) was required. Treatment duration, all-cause and prostate cancer-related HRU, and costs were estimated during the post-index period. Multivariable analyses compared HRU and costs between cohorts, adjusting for baseline characteristics. Results Overall, 920 chemotherapy-naïve patients initiated enzalutamide and 2310 initiated abiraterone acetate (median follow-up, 10.7 and 13.5 months, respectively). More enzalutamide-treated patients had corticosteroid-sensitive comorbidities at baseline. Treatment duration was longer with enzalutamide versus abiraterone acetate (median, 10.7 vs. 8.8 months; P = 0.008). Enzalutamide was associated with fewer all-cause inpatient admissions [adjusted incidence rate ratio (95% confidence interval) 0.87 (0.76, 0.99)], days of hospitalization [0.84 (0.70, 1.02)], and outpatient visits [0.94 (0.90, 0.98)], and fewer prostate cancer-related outpatient visits [0.92 (0.87, 0.96)] compared with abiraterone acetate. Enzalutamide was also associated with lower prostate cancer-related inpatient and emergency department costs [adjusted differences, $122 (P = 0.024) and $28 (P = 0.009), respectively]. Conclusion Chemotherapy-naïve mCRPC patients treated with enzalutamide versus abiraterone acetate had longer treatment duration and incurred lower HRU and prostate cancer-related inpatient and emergency department costs. Funding Astellas Pharma Inc.
      PubDate: 2018-09-06
      DOI: 10.1007/s12325-018-0774-1
  • A Charter to Improve Patient Care in Severe Asthma
    • Authors: Andrew Menzies-Gow; G-Walter Canonica; Tonya A. Winders; Jaime Correia de Sousa; John W. Upham; Antje-Henriette Fink-Wagner
      Abstract: Abstract Severe asthma is a subtype of asthma that is difficult to treat and control. By conservative estimates, severe asthma affects approximately 5–10% of patients with asthma worldwide. Severe asthma impairs patients’ health-related quality of life, and patients are at risk of life-threatening asthma attacks. Severe asthma also accounts for the majority of health care expenditures associated with asthma. Guidelines recommend that patients with severe asthma be referred to a specialist respiratory team for correct diagnosis and expert management. This is particularly important to ensure that they have access to newly available biologic treatments. However, many patients with severe asthma can suffer multiple asthma attacks and wait several years before they are referred for specialist care. As global patient advocates, we believe it is essential to raise awareness and understanding for patients, caregivers, health care professionals, and the public about the substantial impact of severe asthma and to create opportunities for improving patient care. Patients should be empowered to live a life free of symptoms and the adverse effects of traditional medications (e.g., oral corticosteroids), reducing hospital visits and emergency care, the loss of school and work days, and the constraints placed on their daily lives. Here we provide a Patient Charter for severe asthma, consisting of six core principles, to mobilize national governments, health care providers, payer policymakers, lung health industry partners, and patients/caregivers to address the unmet need and burden in severe asthma and ultimately work together to deliver meaningful improvements in care. Funding: AstraZeneca.
      PubDate: 2018-09-04
      DOI: 10.1007/s12325-018-0777-y
  • Neuroplasticity, Neurotransmission and Brain-Related Genes in Major
           Depression and Bipolar Disorder: Focus on Treatment Outcomes in an Asiatic
    • Authors: Marco Calabrò; Laura Mandelli; Concetta Crisafulli; Soo-Jung Lee; Tae-Youn Jun; Sheng-Min Wang; Ashwin A. Patkar; Prakash S. Masand; Francesco Benedetti; Changsu Han; Chi-Un Pae; Alessandro Serretti
      Abstract: Introduction Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. Methods Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6–8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. Results None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT. Discussion Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.
      PubDate: 2018-09-03
      DOI: 10.1007/s12325-018-0781-2
  • Correction to: Patterns of Bicalutamide Use in Prostate Cancer Treatment:
           A U.S. Real-World Analysis Using the SEER-Medicare Database
    • Authors: Jennifer L. Beebe-Dimmer; Julie J. Ruterbusch; Lauren C. Bylsma; Christina Gillezeau; Jon Fryzek; Neil M. Schultz; Scott C. Flanders; Arie Barlev; Elisabeth Heath; Ruben G. W. Quek
      Abstract: The original article can be found online.
      PubDate: 2018-08-16
      DOI: 10.1007/s12325-018-0767-0
  • Treatment and Monitoring Patterns Among Premenopausal Women with
           HR+/HER2− Advanced Breast Cancer
    • Authors: Anand A. Dalal; Geneviève Gauthier; Patrick Gagnon-Sanschagrin; Rebecca Burne; Annie Guérin; Polly Niravath; Tania Small
      Abstract: Introduction Premenopausal women with hormone receptor positive (HR+) and human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (aBC) often present with aggressive tumor types that lead to poor prognosis, high rates of recurrence, and mortality. Although clinical guidelines provide evidence-based recommendations for optimal treatment and monitoring, there is a dearth of information regarding treatment and monitoring patterns in clinical practice. In this study, we describe treatment and monitoring patterns among premenopausal women with HR+/HER2− aBC in real-world practice. Methods A large US claims database was used to describe treatment patterns for patients in first, second, and third lines of therapy. Treatment monitoring included complete blood count (CBC), liver function test (LFT), and electrocardiogram (EKG) monitoring, described for the first three lines of therapy, and separately for patients receiving endocrine monotherapy (ET) and chemotherapy. Results Among 3203 patients, chemotherapy was the most common treatment used in first-line (63.6%) and second-line therapy (66.9%). ET was used in 34.4, 30.1, and 73.6% of patients in first, second, and third lines of therapy, respectively. The two most common treatment sequences were a single line of ET (27.3%), and two consecutive lines of chemotherapy followed by a line of ET (19.3%). Patients receiving chemotherapy were monitored with CBC on average more than two times per month, and for LFT one to two times per month. Patients receiving ET were monitored with CBC and LFT on average once every 2–3 months. Overall, approximately 20% of patients were monitored with an EKG at some point during each line of therapy. Conclusion A considerable proportion of premenopausal women with aBC received first- and second-line chemotherapy, which appears inconsistent with current clinical guidelines. The observed treatment heterogeneity points to a lack real-world consensus on the management of premenopausal women with HR+/HER2− aBC. Funding Novartis Pharmaceuticals Corporation.
      PubDate: 2018-08-13
      DOI: 10.1007/s12325-018-0764-3
  • Correction to: To See or NOsee: The Debate on the Nocebo Effect and
           Optimizing the Use of Biosimilars
    • Authors: Mourad F. Rezk; Burkhard Pieper
      Abstract: The article “To See or NOsee: The Debate on the Nocebo Effect and Optimizing the Use of Biosimilars”, written by Mourad F. Rezk and Burkhard Pieper was originally published electronically on the publisher’s internet portal (currently SpringerLink) on June 5, 2018 without open access.
      PubDate: 2018-08-10
      DOI: 10.1007/s12325-018-0768-z
  • Prostate Cancer in Primary Care
    • Authors: Samuel W. D. Merriel; Garth Funston; Willie Hamilton
      Abstract: Abstract Prostate cancer is a common malignancy seen worldwide. The incidence has risen in recent decades, mainly fuelled by more widespread use of prostate-specific antigen (PSA) testing, although prostate cancer mortality rates have remained relatively static over that time period. A man’s risk of prostate cancer is affected by his age and family history of the disease. Men with prostate cancer generally present symptomatically in primary care settings, although some diagnoses are made in asymptomatic men undergoing opportunistic PSA screening. Symptoms traditionally thought to correlate with prostate cancer include lower urinary tract symptoms (LUTS), such as nocturia and poor urinary stream, erectile dysfunction and visible haematuria. However, there is significant crossover in symptoms between prostate cancer and benign conditions affecting the prostate such as benign prostatic hypertrophy (BPH) and prostatitis, making it very challenging to distinguish between them on the basis of symptoms. The evidence for the performance of PSA in asymptomatic and symptomatic men for the diagnosis of prostate cancer is equivocal. PSA is subject to false positive and false negative results, affecting its clinical utility as a standalone test. Clinicians need to counsel men about the risks and benefits of PSA testing to inform their decision-making. Digital rectal examination (DRE) by primary care clinicians has some evidence to show discrimination between benign and malignant conditions affecting the prostate. Patients referred to secondary care for diagnostic testing for prostate cancer will typically undergo a transrectal or transperineal biopsy, where a number of samples are taken and sent for histological examination. These biopsies are invasive procedures with side effects and a risk of infection and sepsis, and alternative tests such as multiparametric magnetic resonance imaging (mpMRI) are currently being trialled for their accuracy and safety in diagnosing clinically significant prostate cancer.
      PubDate: 2018-08-10
      DOI: 10.1007/s12325-018-0766-1
  • A New Automatically Fixating Stone Basket (2.5 F) Prototype with a
           Nitinol Spring for Accurate Ureteroscopic Stone Size Measurement
    • Authors: Jens Cordes; Felix Nguyen; Wolfhard Pinkowski; Axel S. Merseburger; Tomasz Ozimek
      Abstract: Introduction Intraoperative assessment of stone size is crucial for the successful and safe extraction of stones. The first automatically fixating measuring stone basket prototype showed a mismatch between the steel spring and the nitinol basket; therefore, to improve this prototype, the steel spring was replaced with a nitinol spring and a modified scale was implemented on the basket handle for accurate intraoperative stone size measurement. Methods The proposed tipped basket was composed of nitinol. A standard handle with a spring-supported self-closing mechanism (2.5 F, Urotech®) was used, and a modified nonlinear millimeter scale was established on the handle. The grasping force was provided by the new nitinol spring mechanism in the handgrip. Various colors associated with the stone size were applied on the scale. Results The material difference between the basket and the spring was eliminated. The measuring scale ranged from 2 mm (green) through 5 mm (yellow) to 8 mm (red), and the scale was nonlinear because of the nonlinear relationship between the diameter of the stone and the distance marked on the scale. Conclusion The proposed automatically fixating stone basket with a nitinol spring has the potential to improve the safety and effectiveness of endourological stone retrieval. Further validation of this new scale and basket should follow.
      PubDate: 2018-08-04
      DOI: 10.1007/s12325-018-0761-6
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