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Publisher: Springer-Verlag (Total: 2352 journals)

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Showing 1 - 200 of 2352 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 2)
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: 23, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.752, CiteScore: 3)
Abdominal Imaging     Hybrid Journal   (Followers: 17, 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: 27, 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: 30, 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: 3, SJR: 0.305, CiteScore: 1)
Acta Geophysica     Hybrid Journal   (Followers: 11, 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: 13, 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: 7, SJR: 0.822, CiteScore: 2)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 2, SJR: 0.376, CiteScore: 1)
Acta Neuropathologica     Hybrid Journal   (Followers: 4, SJR: 7.589, CiteScore: 12)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.334, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 3, 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: 25, 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: 18, SJR: 1.005, CiteScore: 2)
Adsorption     Hybrid Journal   (Followers: 5, 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: 57, 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: 32, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 4, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 45, 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: 7)
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: 11, SJR: 0.825, CiteScore: 1)
African Archaeological Review     Hybrid Journal   (Followers: 21, 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: 13, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 9, 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: 9, SJR: 0.772, CiteScore: 1)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 18, SJR: 0.46, CiteScore: 1)
American J. of Dance Therapy     Hybrid Journal   (Followers: 5, 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: 16, 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: 6)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 0.978, CiteScore: 3)
Anatomical Science Intl.     Hybrid Journal   (Followers: 3, 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: 20, 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: 17, 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: 34, 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: 5, SJR: 0.687, CiteScore: 2)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 12)
Annals of Regional Science     Hybrid Journal   (Followers: 8, 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: 15, 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: 9, 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: 44, SJR: 0.571, CiteScore: 2)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 18, SJR: 0.21, CiteScore: 1)
Applied Categorical Structures     Hybrid Journal   (Followers: 4, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 49, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 6, SJR: 0.422, CiteScore: 1)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.733, CiteScore: 3)
Applied Geophysics     Hybrid Journal   (Followers: 9, SJR: 0.488, CiteScore: 1)
Applied Intelligence     Hybrid Journal   (Followers: 13, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 8, 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: 66, SJR: 1.182, CiteScore: 4)
Applied Physics A     Hybrid Journal   (Followers: 10, 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: 22, SJR: 0.225, CiteScore: 0)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 7, SJR: 0.542, CiteScore: 1)
Aquaculture Intl.     Hybrid Journal   (Followers: 26, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 2)
Aquatic Ecology     Hybrid Journal   (Followers: 37, SJR: 0.656, CiteScore: 2)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.591, CiteScore: 1)
Aquatic Sciences     Hybrid Journal   (Followers: 14, 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: 21, 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: 66, 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: 6, SJR: 0.79, CiteScore: 2)
Archives and Museum Informatics     Hybrid Journal   (Followers: 156, SJR: 0.101, CiteScore: 0)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 6, 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: 17, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 9, SJR: 0.644, CiteScore: 2)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 9, 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: 16, 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: 2, 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: 18, 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: 13, 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: 13, SJR: 0.353, CiteScore: 1)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 3, 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: 10)
Asian J. of Criminology     Hybrid Journal   (Followers: 6, SJR: 0.543, CiteScore: 1)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 4, 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  
Astronomy and Astrophysics Review     Hybrid Journal   (Followers: 22, SJR: 3.385, CiteScore: 5)

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Similar Journals
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  [2352 journals]
  • Three Years Down the Road: The Aftermath of the CDC Guideline for
           Prescribing Opioids for Chronic Pain
    • Abstract: The 2016 CDC guidelines for opioid prescribing by primary care physicians have exposed some shortfalls in our thinking about opioid use and stranded many chronic pain patients with inadequate analgesia. Opioid prescribing rates started to decline in 2012, but still remain high. The response from providers to the 2016 guidelines have led to unintended consequences. Some of the CDC guidance seems arbitrary and not supported by evidence (the 90 MME per day cutoff). Patient and prescriber education, the role of buprenorphine (an atypical Schedule III opioid), and abuse-deterrent opioids are not mentioned at all but could play crucial roles in reducing abuse. Opioid use disorder (OUD) is not defined by the guidance which calls on primary care physicians to recognize and treat it. Opioid withdrawal syndrome is not mentioned and tapering plans, although advised, are not described in a practical way. While the morbidity and mortality associated with OUD are public health crises, so is untreated pain. Chronic pain patients deserve consideration, yet emerge as the silent epidemic within the opioid crisis. To be sure, there is much good in the CDC guidance or any guidelines that urge caution and care in opioid prescribing. Pain specialists must speak out to advocate for patients dealing with pain, to educate patients and prescribers about analgesic options, and to make sure that pain is adequately treated particularly in vulnerable populations.
      PubDate: 2019-04-23
  • The Association of Tacrolimus Formulation Switching with Trough
           Concentration Variability: A Retrospective Cohort Study of Tacrolimus Use
           Post-Kidney Transplantation Based on National Drug Code (NDC) Numbers
    • Abstract: Introduction It was hypothesized that patients experiencing at least one tacrolimus formulation switch may require more frequent therapeutic drug monitoring, subsequent dose adjustments, and a potential for untoward clinical outcomes than patients who remain on a single formulation. Methods Eligible patients were adult kidney transplant recipients with stable renal function at month 3 post-transplant and no evidence of acute rejection, receiving an oral, tacrolimus-based regimen. Patients were categorized into two groups (fixed or variable formulation) using the US National Drug Code (NDC) on the basis of tacrolimus formulation usage over the 12-month period. Results A total of 305 patients were enrolled from four US transplant centers; 44 (14.4%) received multiple formulations and 261 (85.6%) received a single formulation. Mean number of tacrolimus dose adjustments and mean cumulative milligram dose change were not statistically different between the two groups. Mean trough-to-dose ratio, frequency of trough level measurements, and mean number of excursions above 120% or below 80% of the patient’s mean trough concentration were significantly higher in the variable compared to the fixed formulation group. Conclusion A variable tacrolimus formulation regimen was associated with a higher frequency of trough level measurements and a greater number of excursions in trough levels compared with continuing on a fixed formulation regimen of tacrolimus in this retrospective chart review study. Funding Astellas Pharma Global Development, Inc. Plain Language Summary Plain language summary available for this article.
      PubDate: 2019-04-19
  • Economic Evaluation of Sarilumab in the Treatment of Adult Patients with
           Moderately-to-Severely Active Rheumatoid Arthritis Who Have an Inadequate
           Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs
    • Abstract: Introduction Assess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg + methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD + methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate. Methods Microsimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care. Results Lifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold. Conclusion In patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks + methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+ methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab + methotrexate or csDMARD active treatment. Funding Sanofi and Regeneron Pharmaceuticals, Inc.
      PubDate: 2019-04-19
  • Adjunctive Agents for Cervical Preparation in Second Trimester Surgical
    • Abstract: Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among the reasons for this is the degree of cervical dilation required to safely extricate fetal parts. Cervical dilation is traditionally achieved by placing multiple sets of osmotic dilators over two or more days prior to the evacuation procedure; however, there is interest in shortening cervical preparation time. The use of adjuvant mifepristone and misoprostol in conjunction with osmotic dilators has been studied for this purpose, and their use demonstrates that adequate cervical dilation can be achieved in less time than with dilators alone. We present a review of the current evidence surrounding adjunctive agents for cervical preparation, and contend that for women presenting for surgical abortion care above 19 weeks gestation, the use of adjunctive mifepristone and/or misoprostol should be strongly considered along with osmotic dilator insertion when cervical preparation in less than 24 h is needed.
      PubDate: 2019-04-19
  • Study Protocol for a Prospective, Multicenter, Randomized, Open-Label,
           Parallel-Group Clinical Trial Comparing the Efficacy and Safety of a
           Needle-Free Insulin Injector and a Conventional Insulin Pen in Controlling
           Blood Glucose Concentrations in Chinese Patients with Type 2 Diabetes
           Mellitus (The FREE Study)
    • Abstract: Introduction China has the largest number of diabetic patients in the world. In the past 2 decades, the prevalence of diabetes in China has increased dramatically, and the current status of diabetes control in the diabetic population is not satisfactory. Although insulin is currently recognized in diabetes treatment guidelines as the therapeutic option for patients not adequately controlled by diet/exercise and oral agents, the proportion of patients with type 2 diabetes using insulin is still very low, and the time when insulin therapy is initiated is relatively late. In using insulin injections, concerns about the complexity of the treatment regimen, a fear of needles, and other psychological barriers can affect insulin treatment, impacting on patient compliance and potentially resulting in a poor treatment response. Another type of insulin injection device that has become available recently, the needle-free injector, is now being used in clinical practice because of its unique features and patients’ injection experiences. The aims of this study are to investigate the efficacy and safety of the needle-free injector-based insulin treatment in blood glucose control in patients with type 2 diabetes, as compared with a conventional needle-based insulin treatment, and to evaluate patient satisfaction with the different insulin delivery methods. Methods and Planned Outcomes A prospective, multicenter, randomized, open-label, parallel-group clinical trial was designed and implemented in China. A total of 420 patients with type 2 diabetes from ten research centers will be enrolled in the study. The primary efficacy endpoint is the change in the glycosylated hemoglobin (HbA1c) level from baseline to after 16 weeks of treatment after randomization. Secondary efficacy endpoints include measurements of blood glucose concentrations, the rate of achieving the target HbA1c level of less than 7%, patients’ quality-of-life (as determined by the SF-36 questionnaire), the insulin dose administered, compliance with insulin therapy, and patients’ satisfaction with their injection device. Ethics and Dissemination The study was approved by the Independent Ethics Committee (IEC) of Peking University Peoples Hospital and was conducted in accordance with the moral, ethical, and scientific principles of the declaration of Helsinki and the provisions of good clinical practice (GCP) in China. Written informed consent will be obtained from all participants before any study-related procedures are implemented. It is hoped that the study will provide evidence for the clinical application of the needle-free injector by providing data on its efficacy and safety, as compared with a conventional insulin pen, in the Chinese type 2 diabetes population. When available, the results will be published in an international peer-reviewed journal. Trial Registration Identifier, NCT03243903. Registration date, August 9, 2017. Funding Beijing QS Medical Technology Co., Ltd.
      PubDate: 2019-04-19
  • Correction to: A Relative Cost of Control Analysis of Once-Weekly
           Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing
           Patients to HbA1c and Weight Loss Treatment Targets in the USA
    • Abstract: The article “A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA”, written by Pierre Johansen, Barnaby Hunt, Neeraj N. Iyer, Tam Dang-Tan, Richard F. Pollock was originally published electronically on the publisher’s internet portal (currently SpringerLink) on November 27, 2018 without Open Access.
      PubDate: 2019-04-12
  • Anti-MEK and Anti-EGFR mAbs in RAS-Mutant Metastatic Colorectal Cancer:
           Case Series and Rationale
    • Abstract: KRAS (Kirsten rat sarcoma viral oncogene) or BRAF (v-raf murine sarcoma viral oncogene homolog B1) constitutive activation leads to anti-EGFR (epidermal growth factor receptor) therapy resistance of metastatic colorectal cancer patients. In this article we investigate the effects of anti-MEK (mitogen-activated protein kinase) antibody (trametinib) combined with anti-EGFR (cetuximab) on colon cancer cell lines with different RAS statuses. Even though cetuximab has no effect on RAS cell viability and ERK (extracellular-signal-regulated kinase) phosphorylation (one of the last kinases of the EGFR pathway), trametinib can induce cell death and inhibit the activation of ERK alone or in combination with cetuximab. In a more pathologic context, we observed that KRAS colon cancer patient biopsies treated ex vivo with trametinib and cetuximab also present less ERK phosphorylation. Finally, nine ovarian, endometrial and colon cancer patients with different KRAS statuses were treated with anti-EGFR/anti-MEK combination off label after molecular tumor board decision. KRAS exon 2 patients have significantly longer PFS (progression-free survival) than with previous lines of treatments. We believe that such observations provide a rationale for designing a clinical trial to test this association in RAS exon 2 mutated cancers.
      PubDate: 2019-04-12
  • Comparison of Doppler-Guided Transanal Hemorrhoidal Dearterialization for
           Grade III and IV Hemorrhoids in Vietnam
    • Abstract: Introduction This study aimed to assess the short- and long-term outcomes of Doppler-guided transanal hemorrhoidal dearterialization (THD) for grade III and IV hemorrhoidal disease in Vietnam. Methods In a prospective observational design, patients treated for grade III and IV hemorrhoidal disease with the THD method at the National Hospital of Traditional Medicine (Hanoi, Vietnam) were included between June 2012 and December 2013. Patients were evaluated postoperatively at the time they were discharged from the hospital (short-term outcome) and 6 months after surgery (long-term outcome). Results A total of 128 patients were enrolled in the study, 94 were classified with grade III disease and 34 with grade IV. Grade IV hemorrhoidal patients reported on average 18.2 years of disease symptom duration, while grade III hemorrhoidal patients reported 11.2 years. All patients with grade III and grade IV hemorrhoidal disease had good outcomes at discharge day and reported to return to work in a median of 6 days after THD. At long-term follow-up, the results were good for 80.9% of patients from grade III hemorrhoidal disease and 61.8% of patients from grade IV hemorrhoidal disease. Patient satisfaction with the procedure and outcomes was 93.6% for grade III and 85.3% for grade IV hemorrhoidal patients. Conclusions The THD technique was shown to be safe for both grade III and IV hemorrhoidal patients. The THD technique showed better results with grade III hemorrhoidal patients as compared to grade IV hemorrhoidal patients.
      PubDate: 2019-04-10
  • Gender Effects in the Efficacy of Racemic Amphetamine Sulfate in Children
           with Attention-Deficit/Hyperactivity Disorder
    • Abstract: Introduction A laboratory classroom study in children aged 6–12 years with attention-deficit/hyperactivity disorder (ADHD) found that racemic amphetamine sulfate (RA-AMPH) significantly improved performance versus placebo from 45 min through 10 h post-dose (NCT01986062). A secondary analysis assessed gender as a potential moderator of response to treatment comparing the ADHD Rating Scale-IV (ADHD-RS-IV) and Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) rating scales. Methods After 8 weeks of open-label RA-AMPH dose optimization using improvement in ADHD-RS-IV symptoms as a guide, 97 subjects (38 females and 59 males) were randomized to the sequence of 2 weeks of double-blind treatment with the optimized dose of RA-AMPH followed by placebo or vice versa during a laboratory classroom day. Efficacy measures included the SKAMP and the Permanent Product Measure of Performance (PERMP). The average difference for RA-AMPH versus placebo was estimated using least-square (LS) means. Treatment interaction by gender was analyzed using a cross-sectional fixed-effects model. Results ADHD-RS-IV scores were comparable for males and females at study entry and at the end of open-label treatment. During double-blind treatment, LS mean scores significantly improved for both genders versus placebo on the SKAMP scale and the PERMP (average p < 0.0001 for all post-dose time points). Beginning at baseline, males had significantly higher (worse) SKAMP scores than females but not worse ADHD-RS-IV or PERMP scores. Conclusion Both genders responded well to treatment with RA-AMPH, with comparable onset and duration of effect. The ADHD-RS-IV and SKAMP scales both measure changes in attention and hyperactive-impulsive behavior, but the SKAMP scale also measures associated disruptive behaviors, such as frustration, lying, and interpersonal conflict, that are more characteristic of oppositional and conduct disorders and more prevalent in boys with ADHD. Therefore, the SKAMP may be more sensitive for measuring the range of symptoms of boys with ADHD than the ADHD-RS-IV. Funding Arbor Pharmaceuticals, LLC.
      PubDate: 2019-04-10
  • Efficacy of Triamcinolone Acetonide Extended-Release in Participants with
           Unilateral Knee Osteoarthritis: A Post Hoc Analysis
    • Abstract: Introduction Osteoarthritis (OA) is common and its prevalence is increased in military service members. In a phase 3 randomized controlled trial (NCT02357459), a single intra-articular injection of an extended-release formulation of triamcinolone acetonide (TA-ER) in participants with unilateral or bilateral knee OA demonstrated substantial improvement in pain and symptoms. Bilateral knee pain has emerged as a confounding factor in clinical trials when evaluating the effect of a single intra-articular injection. Furthermore, unilateral disease is frequently first to emerge in active military personnel secondary to prior traumatic joint injury. In this post hoc analysis, we assessed efficacy and safety of TA-ER in a subgroup of participants with unilateral knee OA. Methods Participants ≥ 40 years of age with symptomatic knee OA were randomized to a single intra-articular injection of TA-ER 32 mg, TA crystalline suspension (TAcs) 40 mg, or saline-placebo. Average daily pain (ADP)-intensity and rescue medication use were collected at each of weeks 1–24 postinjection; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain), WOMAC-B (stiffness), WOMAC-C (function), and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QoL) were collected at weeks 4, 8, 12, 16, 20, and 24 postinjection. Adverse events (AEs) were assessed throughout the study. Participants with unilateral knee OA were selected for this analysis. Results Of 170 participants with unilateral OA (TA-ER, N = 51; saline-placebo, N = 60; TAcs, N = 59), 42% were male and 89% were white. TA-ER significantly (p < 0.05) improved ADP-intensity vs. saline-placebo (weeks 1–24) and TAcs (weeks 4–21). TA-ER significantly (p < 0.05) improved WOMAC-A vs. saline-placebo (all time points) and TAcs (weeks 4, 8, 12, 24). Consistent outcomes were observed for rescue medication, WOMAC-B, WOMAC-C, and KOOS-QoL. AEs were similar in frequency/type across treatments. Conclusion TA-ER provided 5–6 months’ pain relief that consistently exceeded saline-placebo and TAcs, suggesting that TA-ER injected intra-articularly into the affected knee may be an effective non-opioid treatment option. Although the participants included in this analysis did not fully represent the diverse demographics of active service members, the substantial unmet medical need in the military population suggests that TA-ER may be an important treatment option; additional studies of TA-ER in active military patients are needed. Trial Registration NCT02357459. Funding Flexion Therapeutics, Inc. Plain Language Summary Plain language summary available for this article.
      PubDate: 2019-04-09
  • Indirect Comparison of Ropinirole and Pramipexole as Levodopa Adjunctive
           Therapy in Advanced Parkinson’s Disease: A Systematic Review and Network
    • Abstract: Introduction To evaluate the comparative efficacy and safety of ropinirole and pramipexole as adjunctive therapies to levodopa (l-dopa) for the management of advanced Parkinson’s disease (PD), via a systematic review and network meta-analysis. Methods Twenty-one double-blind randomised controlled trials of patients with advanced PD with motor fluctuations receiving l-dopa comparing ropinirole or pramipexole with comparators were identified from 2550 publications. Bayesian indirect comparison methods were applied to independently review efficacy outcomes including off-time reduction, Unified Parkinson's Disease Rating Scale-Activity of Daily Living (UPDRS-ADL) and UPDRS-motor scores, and safety outcomes including adverse events (AE) and patient withdrawals, to determine indirect treatment comparison mean differences (MD) or hazard ratios (HR) with 95% confidence intervals (CI). Results The indirect efficacy comparison resulted in a statistically nonsignificant off-time reduction difference (hours) of ropinirole-sustained release (SR) versus pramipexole-immediate release (MD − 0.25; 95% CI − 0.71, 0.21) and ropinirole-SR versus pramipexole-extended release (ER) (MD 0.18; 95% CI − 0.40, 0.76). Ropinirole-SR adjunctive treatment showed a tendency towards more improvement in UPDRS-ADL score (MD 1.24; 95% CI 0.23, 2.24) than adjunctive treatment of pramipexole-ER. Pramipexole-ER may be less likely to induce somnolence as an AE compared with ropinirole-SR (HR 0.46; 95% CI 0.23, 0.89). However, there were no statistically significant differences in UPDRS-motor score reduction, incidence of dyskinesia, hallucination, hypotension, insomnia and nausea, or withdrawals due to AE, for any reason. Conclusion Adjunctive therapy with ropinirole-SR or pramipexole appears to offer similar efficacy and tolerability in patients with advanced PD on the basis of this indirect comparison. Funding GSK
      PubDate: 2019-04-08
  • Observational Prospective Study to Determine the Evolution of the
           Symptomatic Profile of Metastatic Non-Small Cell Lung Cancer (NSCLC)
           Patients and Its Relation to the Control of the Disease
    • Abstract: Objective To evaluate the evolution of disease-related symptoms and its relationship with the control of the disease in first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). Methods This was an observational, prospective, national and multicentre study with two visits in which the following were collected: (1) baseline visit: sociodemographic and clinical variables (2) visit after completing the 4–6 chemotherapy cycles: criteria for ending treatment, control of the disease and clinical variables. Ad hoc questionnaires were collected to assess the frequency of symptoms (evaluated by the patient), and quality-of-life questionnaires to assess the intensity of symptoms (using the Lung Cancer Symptom Scale, LCSS), and interference in the patient’s daily life, assessed by the patient and by the investigator. Results A total of 155 patients were included. Patients predominantly described tiredness (24.1%) and pain (23.9%) as the symptoms that appeared “frequently or continuously”. A statistically significant decrease in scores for symptoms of cough (15.4 points), dyspnoea (8.5 points), pain (9.5 points) and discomfort related to their illness (9 points) was observed between visits. Patients who achieved a complete or partial response showed a statistically significant reduction in the cough, dyspnoea, pain and disconfort frequency. Regarding the intensity, cough was the only symptom that showed  a statistically significant decrease for both the patient and the investigator. Tiredness/asthenia and pain were the symptoms with the greatest interference in daily life at baseline according to the patient; however, according to the investigator, they were mood and quality/quantity of sleep, although none of them were significant. But changes in the score of the interference questionnaire between visits were not statistically significantly related to the control of the disease. However, average score according to both investigator and patients showed a significant correlation with ECOG status. Conclusion The first-line treatment of NSCLC is correlated with an improvement in the symptomatic evolution of advanced NSCLC patients. Funding Roche.
      PubDate: 2019-04-08
  • Outcomes Associated with Treatment of Chronic Pain with Tapentadol
           Compared with Morphine and Oxycodone: A UK Primary Care Observational
    • Abstract: Introduction This study compared adverse outcomes and resource use for patients with a diagnosis of pain treated with tapentadol prolonged-release (PR) versus those treated with morphine controlled-release (CR) and oxycodone CR. Methods Data were sourced from the Clinical Practice Research Datalink (CPRD), a database derived from UK primary care. Patients prescribed tapentadol PR between May 2011 and December 2016 were selected and matched to two groups of controls treated with either morphine CR or oxycodone CR on gender, age, pain duration, pain site, pain aetiology, Charlson index and prior analgesia. Times to first adverse event (constipation or nausea/vomiting) were compared within a Cox proportional hazards model. Rates of primary care contacts, accident and emergency contacts and, for a subset of patients linked to Hospital Episode Statistics (HES), inpatient admissions and outpatient contacts were compared using incidence rate ratios (IRRs) derived from Poisson regression. Results A total of 1907 patients prescribed tapentadol PR were identified and 1791 (93.9%) had a pain diagnosis. Of these 1246 (65.3%) were matched to morphine controls and 829 (43.4%) to oxycodone controls. Compared to controls, gastrointestinal adverse events with tapentadol PR treatment were reduced; aHR = 0.532 (0.402–0.703; p < 0.001) versus morphine CR and 0.517 (0.363–0.735; p < 0.001) versus oxycodone CR. Compared with morphine CR, primary care contacts [IRR = 0.831 (0.802–0.861)], accident and emergency attendance [0.739 (0.572–0.951)], outpatient contacts [0.917 (0.851–0.989)] and inpatients contacts [0.789 (0.664–0.938)] were reduced. For oxycodone, the respective figures were 0.735 (0.703–0.768), 0.971 (0.699–1.352), 0.877 (0.799–0.962) and 0.748 (0.601–0.932). Conclusion Tapentadol PR was associated with significantly fewer adverse gastrointestinal events than morphine CR and oxycodone CR in patients with a diagnosis of pain. There was also significantly reduced primary and secondary care resource use. As with all observational studies, potential bias due to residual confounding and confounding by indication should be considered. Funding Grünenthal Ltd.
      PubDate: 2019-04-08
  • Roxadustat Treatment of Chronic Kidney Disease-Associated Anemia in
           Japanese Patients Not on Dialysis: A Phase 2, Randomized, Double-Blind,
           Placebo-Controlled Trial
    • Abstract: Introduction This study evaluated efficacy and safety/tolerability of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in Japanese anemic non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. Methods In this phase 2, double-blind, 24-week study, NDD-CKD patients were randomized to oral placebo or roxadustat (50, 70, or 100 mg) three times weekly (TIW) for 6 weeks followed by dose adjustments to maintain hemoglobin (Hb) at 10–12 g/dL for 18 weeks; patients meeting pre-defined criteria were re-randomized to TIW or once-weekly dosing. The primary end point was rate of rise of Hb (g/dL/week) during the first 6 weeks; secondary end points included response rate (Hb ≥ 10.0 g/dL and increase in Hb from baseline ≥ 1 g/dL) and mean Hb and change from baseline in Hb at weeks 18–24. The main safety outcomes were vital signs, laboratory test results, electrocardiograms, and frequency of treatment-emergent adverse events. Results Of 107 patients randomized, 83 completed the study. The mean (SD) rate of rise of Hb during the first 6 weeks was − 0.052 (0.142) for placebo and + 0.200 (0.160), + 0.453 (0.256), and + 0.570 (0.240) for roxadustat 50-, 70-, and 100-mg TIW groups, respectively (p < 0.001). Response rate was 14.8% for placebo and 81.5%, 100%, and 100% for roxadustat TIW groups (p < 0.001). Change in Hb from baseline at weeks 18–24 was − 0.17 (0.61) for placebo and + 1.10 (0.71), + 1.33 (0.82), and + 1.55 (0.88) g/dL for roxadustat TIW groups (p < 0.001). No deaths or major adverse cardiac events occurred with roxadustat. Conclusion Roxadustat was well tolerated and effective in correcting Hb levels within 6 weeks in Japanese anemic NDD-CKD patients. Trial registration NCT01964196. Registered 15 October 2013 (retrospectively registered). Funding Astellas Pharma Inc.
      PubDate: 2019-04-05
  • A 48-Week, Multicenter, Open-Label, Observational Study Evaluating Oral
           Rivastigmine in Patients with Mild-to-Moderate Alzheimer’s Disease in
    • Abstract: Introduction Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer’s type. This study assessed the short- and long-term effectiveness and safety of rivastigmine in patients with mild-to-moderate Alzheimer’s disease (AD) in a real-world clinical setting in Taiwan. Methods This was a 48-week, single-arm, open-label, prospective, observational, post-marketing surveillance, multicenter study. The primary outcomes were change from baseline to week 48 in the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scores. One-year persistence to treatment, effect on activities of daily living, and incidence of adverse events (AEs) were also assessed. Results Overall, 151 patients were enrolled in the study, of which 91 (60.26%) completed this study. At the end of the study, the mean rivastigmine dose received by the patients was 6.59 mg/day. At week 48, the changes in mean [standard deviation (SD)] MMSE and CDR scores in the intent-to-treat (ITT) population from baseline were − 1.00 (3.8; p = 0.0344) and 0.07 (0.29; p = 0.0403), respectively. The most frequently reported AEs by preferred term were dizziness (12.58%) and nausea (9.27%). No new or unexpected AEs were observed, and 30 (20.13%) patients in the ITT population were on rivastigmine therapy for 1 year without treatment discontinuation. Conclusion Despite the low 1-year persistence rate, rivastigmine showed a stabilizing effect on declining cognition in patients with mild-to-moderate AD in a real-world scenario. Rivastigmine is well tolerated at 6.0–9.0 mg/day with no unexpected safety concerns. Funding Novartis Co. Ltd., Taipei, Taiwan.
      PubDate: 2019-04-05
  • Prevalence and Control of Dyslipidemia in Patients Referred for High Blood
           Pressure: The Disregarded “Double-Trouble” Lipid Profile in
    • Abstract: Introduction We evaluated the prevalence and control of dyslipidemia in a wide sample of patients referred to our ESH “Hypertension Excellence Centre” for high blood pressure (BP). Furthermore, we evaluated the role of adiposity on the serum lipid profile. Methods Observational study on 1219 consecutive outpatients with valid ambulatory BP monitoring (ABPM) referred for high BP. Patients with body mass index (BMI) ≥ 25 kg/m2 were defined as overweight/obese (OW/OB). Dyslipidemia and the control rates of low-density lipoprotein cholesterol (LDLc) were defined according to the 2016 ESC/EAS Guidelines. Results Mean age: 56.5 ± 13.7 years. Male prevalence: 55.6%. OW/OB patients were 70.2%. The prevalence of dyslipidemia was 91.1%. Lipid-lowering drugs were taken by 23.1% of patients. Patients with controlled LDLc comprised 28.5%, while BP was controlled in 41.6% of patients. Only 12.4% of patients had both 24-h BP and LDLc controlled at the same time. The higher the cardiovascular (CV) risk was, the lower was the rate of LDLc control (p < 0.001). Patients in secondary prevention had worse LDLc control than patients in primary prevention (OR 3.5 for uncontrolled LDLc, p < 0.001). OW/OB showed a more atherogenic lipid profile, characterized by lower high-density lipoprotein cholesterol (HDLc) (p < 0.001), higher non-HDLc (p = 0.006), higher triglycerides (p < 0.001), higher non-HDLc/HDLc (p < 0.001) and higher (non-HDLc + non-LDLc) (p < 0.001). Conclusion Dyslipidemia is still too often neglected in hypertensives, especially in patients at higher CV risk. OW/OB hypertensives have a “double-trouble” atherogenic lipid pattern likely driven by adiposity. We encourage a comprehensive evaluation of the lipid profile in all hypertensives, especially if they are OW/OB, to correctly assess their CV risk and improve their management. Funding Article processing charges funded by Servier SpA.
      PubDate: 2019-04-05
  • Metastatic Renal Cell Cancer: An Analysis of Reimbursement Decisions
    • Abstract: Introduction Metastatic renal cell carcinoma is a complex cancer for which several drugs have been developed over the years. More recently, drugs that target the specific cancer cell mutations have been developed for metastatic cell carcinoma. However, even with the recent influx of targeted therapy options, significant unmet needs exist in around half of treated renal cell carcinoma patients following the failure of first-line therapy. The aim of this study was to review the health technology appraisals of renal cell carcinoma treatments in several countries to establish what factors might affect the reimbursement decisions. Methods The reimbursement data for 10 drugs in several countries were collated from the health technology assessment bodies for each country. The data included information on clinical trials used in the submission documents for the health technology assessment, the reimbursement decisions and the reasons for those decisions, as well as any specific restrictions for use of any of the included drugs. Results Of the 10 drugs reviewed, only everolimus received a positive reimbursement decision by all the health technology assessment bodies included in the study. The most common reason for a negative reimbursement decision was lack of demonstration of cost-effectiveness of the drugs. Another frequently cited reason was unproven clinical efficacy and poor impact on overall survival. Conclusion Despite the many treatment guidelines and current treatment options that are available for renal cell carcinoma, there remains an unmet need in patients with metastatic renal cell carcinoma. On the basis of this analysis, the key reason for a drug not obtaining a positive reimbursement decision is due to poor efficacy or uncertainty of the drug’s efficacy. Funding Eisai, Inc.
      PubDate: 2019-04-05
  • A Multicenter, Observational, Prospective Study of the Effectiveness of
           Switching from Budesonide/Formoterol Turbuhaler ® to
           Budesonide/Formoterol Easyhaler ®
    • Abstract: Introduction In real-life practice, asthma remains poorly controlled, with a considerable burden on patients’ quality of life. Budesonide/formoterol (B/F) Easyhaler® has demonstrated similar dose consistency, therapeutic equivalence, and equivalent bronchodilator efficacy to B/F Turbuhaler®, but no real-life comparisons are yet available in patients switching from B/F Turbuhaler® to B/F Easyhaler®. Methods The primary objective of this real-life, non-interventional, observational study was to show non-inferiority of asthma control when adult patients in Swedish primary care with persistent asthma switched from B/F Turbuhaler® to B/F Easyhaler®. At visit 1, baseline demographic and endpoint data were recorded, and eligible patients switched to B/F Easyhaler®. The study comprised a control visit (visit 2) and a concluding examination (visit 3) after 12 weeks. Asthma control was assessed using the Asthma Control Test (ACT). The mini-Asthma Quality of Life Questionnaire (AQLQ) and lung function test were performed, and participants and investigators answered questionnaires about ease-of-use and teaching. Results A total of 117 patients were enrolled in the on-treatment population; 81 (64.8%) were female. At visit 3, B/F Easyhaler® demonstrated non-inferiority to B/F Turbuhaler®; the mean difference in change from baseline ACT was statistically significant (19.0 vs. 20.8, respectively; p < 0.0001) and met the non-inferiority criteria of B/F Easyhaler® being greater than − 1.5 points versus the reference product. Asthma was well controlled in 62 (53.0%) patients at baseline, increasing to 83 patients (70.9%) at visit 3. Patients experienced statistically significant improvements in mini-AQLQ score after B/F Easyhaler® treatment and lung function remained stable across the treatment period. B/F Easyhaler® was easy to learn and prepare for use. Conclusion This real-life, non-interventional, non-inferiority study in adults with persist asthma demonstrates equivalent or better disease control when patients switch from B/F Turbuhaler® to B/F Easyhaler®. A further study with direct comparison between treatments could add to the understanding of inhaler switch. Funding Orion Corporation, Orion Pharma.
      PubDate: 2019-04-02
  • Integrating Osimertinib in Clinical Practice for Non-Small Cell Lung
           Cancer Treatment
    • Abstract: Treatment of non-small cell lung cancer (NSCLC) is evolving with the use of precision medicine for patients with sensitizing epidermal growth factor receptor (EGFR) mutation. First- and second-generation EGFR tyrosine kinase inhibitors (TKIs) remained the standard of care for patients with EGFR-mutated advanced NSCLC for about a decade. However, treatment resistance eventually develops for most patients who experience initial response to these agents. The most commonly acquired resistance mechanism is the T790M gatekeeper mutation. Poor drug penetration leading to central nervous system (CNS) relapse and dose-limiting toxicities are other concerns. The third-generation EGFR-TKI osimertinib, initially approved as the second-line treatment for patients with T790-mutant NSCLC, demonstrated survival benefits in TKI-naïve EGFR-mutated patients, especially in patients with CNS metastasis. The FLAURA study has shown statistically significant progression-free survival benefit and prolongation of all post-progression outcome endpoints, time to first subsequent therapy, second subsequent therapy, and second progression on subsequent treatment, along with acceptable toxicity and better quality of life outcomes. These data favor osimertinib in the first-line setting for EGFR-mutated NSCLC. This is an important milestone since sequencing the TKI therapy based on accurate prediction of T790M is clinically challenging. In countries like India, T790M testing is not routinely conducted and two-thirds of patients with NSCLC do not receive any second-line therapy. Osimertinib can be administered pragmatically as a first-line therapy. Mature overall survival data from the FLAURA study will be important and could help define the optimal personalized treatment for patients with advanced NSCLC. Funding: AstraZeneca Pharma India Ltd.
      PubDate: 2019-04-02
  • Real-World Study of Once-Daily, Extended-Release Tacrolimus Versus
           Twice-Daily, Immediate-Release Tacrolimus in Kidney Transplantation:
           Clinical Outcomes and Healthcare Resource Utilization
    • Abstract: Introduction Real-world data with extended-release tacrolimus (ER-T) are lacking in the USA. This study examined clinical outcomes and healthcare resource utilization in kidney transplant patients receiving ER-T in clinical practice. Methods This was a retrospective, single-center analysis (February–June 2016) using data from Northwestern University’s Enterprise Data Warehouse. Adult patients receiving a kidney transplant in the preceding 4 years, treated de novo or converted to ER-T from immediate-release tacrolimus (IR-T) within 10 days post-transplantation, and maintained on ER-T (at least 3 months) were included. Patients were matched for demographic and clinical characteristics with IR-T-treated control patients. Endpoints included clinical outcomes and healthcare resource utilization up to 1 year post-transplantation. Results A total of 19 ER-T-treated patients were matched with 55 IR-T-treated patients. No ER-T-treated patients experienced biopsy-confirmed acute rejection (BCAR) or graft failure versus 3 (5.5%) and 3 (5.5%) IR-T-treated patients, respectively. Mean estimated glomerular filtration rate (eGFR), the number of all-cause outpatient visits, readmissions, and all-cause hospitalization days were comparable between groups. Tacrolimus trough levels, days to target level (6–10 ng/mL), and number of required dose adjustments were also similar. Conclusion Real-world clinical outcomes and healthcare resource utilization were similar with ER-T and IR-T. Larger studies will need to investigate the trend toward fewer BCAR events, and increased graft survival with ER-T. Funding Astellas Pharma Global Development, Inc. Plain Language Summary Plain language summary available for this article.
      PubDate: 2019-04-02
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