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Publisher: Springer-Verlag (Total: 2351 journals)

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Showing 1 - 200 of 2351 Journals sorted alphabetically
3D Printing in Medicine     Open Access  
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: 14, 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: 23, 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: 26, 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: 6, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.305, 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 Parasitologica     Hybrid Journal   (Followers: 10, SJR: 0.641, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 14, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 7, 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: 52, 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: 29, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 43, 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: 5, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Hybrid Journal   (Followers: 19, 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: 28, 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: 10, 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: 3, 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: 63, 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: 23, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 1)
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: 8, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 2, 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: 142, 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: 5, 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: 14, 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: 5, 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  [2351 journals]
  • Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart
    • Authors: Sanjay Kalra; Stephen Atkin; Antonio Cervera; Ashok Kumar Das; Ozgur Demir; Tevfik Demir; Md. Fariduddin; Khoa Tuan Vo; Bon Jeong Ku; Ajay Kumar; Zafar A. Latif; Rachid Malek; Bien J. Matawaran; Roopa Mehta; Nam Quang Tran; Araceli Panelo; Sundeep Ruder; Joel Rodriquez Saldana; Khalid A. Shaikh; Amit Shakya; Dina Shrestha; A. G. Unnikrishnan
      Pages: 928 - 936
      Abstract: Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4–5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.
      PubDate: 2018-07-01
      DOI: 10.1007/s12325-018-0712-2
      Issue No: Vol. 35, No. 7 (2018)
  • Correction to: Multinational Consensus: Insulin Initiation with Insulin
           Degludec/Aspart (IDegAsp)
    • Authors: Sanjay Kalra; Stephen Atkin; Antonio Cervera; Ashok Kumar Das; Ozgur Demir; Tevfik Demir; Md. Fariduddin; Khoa Tuan Vo; Bon Jeong Ku; Ajay Kumar; Zafar A. Latif; Rachid Malek; Bien J. Matawaran; Roopa Mehta; Nam Quang Tran; Araceli Panelo; Sundeep Ruder; Joel Rodriquez Saldana; Khalid A. Shaikh; Amit Shakya; Dina Shrestha; A. G. Unnikrishnan
      Pages: 937 - 938
      Abstract: Unfortunately, the fifth author name was incorrectly published in the original publication. The correct name should read as ‘Ozgur Demir’.
      PubDate: 2018-07-01
      DOI: 10.1007/s12325-018-0728-7
      Issue No: Vol. 35, No. 7 (2018)
  • Correction to: Combination Glucose-Lowering Therapy Plans in T2DM:
           Case-Based Considerations
    • Authors: Lawrence Blonde; Susana Dipp; Daniel Cadena
      Pages: 966 - 966
      Abstract: The article “Combination Glucose-Lowering Therapy Plans in T2DM: Case-Based Considerations”.
      PubDate: 2018-07-01
      DOI: 10.1007/s12325-018-0729-6
      Issue No: Vol. 35, No. 7 (2018)
  • The Effectiveness of Trimetazidine Treatment in Patients with Stable
           Angina Pectoris of Various Durations: Results from the CHOICE-2 Study
    • Authors: Maria Glezer; on behalf of the CHOICE-2 study investigators
      Pages: 1103 - 1113
      Abstract: Introduction Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease. Methods CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina. Results A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration. Conclusion TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life. Funding Servier. Trial Registration ISRCTN identifier ISRCTN65209863. Plain Language Summary Plain language summary available for this article.
      PubDate: 2018-07-01
      DOI: 10.1007/s12325-018-0674-4
      Issue No: Vol. 35, No. 7 (2018)
  • Comparison of Characteristics of Benign Prostatic Hyperplasia (BPH)
           Patients Treated with Finasteride and Alpha Blocker Combination Therapy
           Versus Alpha Blocker Monotherapy in China: An Analysis of Electronic
           Medical Record Data
    • Authors: Yanyan Fu; Simeng Han; Li Wang; Wei Gao; Eric Wu; Xian Cao; Jianye Wang
      Abstract: Introduction Benign prostatic hyperplasia (BPH) is commonly treated with 5-alpha-reductase inhibitor/alpha blocker combination therapy or with alpha blocker monotherapy. However, in China, the characteristics of BPH patients receiving 5-alpha-reductase inhibitor/alpha blocker combination therapy or alpha blocker monotherapy remain largely unknown. Therefore, this study compared the characteristics of BPH patients receiving either the 5-alpha-reductase inhibitor finasteride in combination with an alpha blocker or an alpha blocker as monotherapy in clinical practice in China. Methods Data were obtained from a large electronic medical record database from four tertiary hospitals in major cities in China (2009–2016). BPH patients aged ≥ 50 years with ≥ 1 alpha blocker fill on/after the first BPH diagnosis were selected. Patients were further classified as receiving combination therapy (≥ 1 overlapping day of supply for finasteride and an alpha blocker) or alpha blocker monotherapy (did not receive any 5-alpha-reductase inhibitor). Patient characteristics, visit type (in- vs. outpatient) at treatment initiation, and comorbidities were evaluated during the 6-month baseline period and compared between the two groups using two sample t tests and chi-square tests/Fisher’s exact tests. Results A total of 2666 and 2738 patients received combination therapy and monotherapy, respectively. The combination group was older (70.3 vs. 67.3 years, p < 0.0001) and had more patients initiated in an inpatient setting (46.0% vs. 26.4%, p < 0.0001). Compared with the monotherapy group, the combination group had more comorbidities, such as hypertension (48.3% vs. 35.6%, p < 0.0001), cardiovascular disease (65.3% vs. 48.0%, p < 0.0001), and diabetes (21.1% vs. 15.7%, p < 0.0001), and a higher Charlson comorbidity index (0.9 vs. 0.7, p < 0.0001). Conclusion Chinese BPH patients using finasteride/alpha blocker combination therapy were older and had a higher comorbidity burden than those using alpha blocker monotherapy. These findings provide Chinese healthcare decision-makers with a better understanding of the patient characteristics generally associated with BPH combination therapy vs. alpha blocker monotherapy. Funding Merck Sharp and Dohme (China) Co., Ltd., Shanghai, China.
      PubDate: 2018-07-16
      DOI: 10.1007/s12325-018-0748-3
  • Total Joint Arthroplasty in Patients with Inflammatory Rheumatic Diseases
    • Authors: Riccardo Compagnoni; Roberta Gualtierotti; Pietro Randelli
      Abstract: Since its introduction, total joint arthroplasty (TJA) has improved the quality of life of patients with degenerative joint disorders. In the last decades, a number of conventional and biological disease-modifying antirheumatic drugs have become available for the treatment of patients with inflammatory rheumatic diseases (IRD), leading to a reduction in the need to undergo TJA. However, TJA is still frequently performed in IRD patients. Both rheumatologists and orthopedics should be aware that patients with IRD have a peculiar perioperative risk profile due to disease-related, patient-related, and surgery-related risk factors. On the basis of current evidence, TJA is a safe procedure for IRD patients as long as an accurate risk stratification and a multidisciplinary approach are applied. We here describe the current strategies for an appropriate surgical management of osteoarthritis in IRD patients and the fascinating opening perspectives that surgeons and clinicians may expect in the future.
      PubDate: 2018-07-11
      DOI: 10.1007/s12325-018-0750-9
  • Enhanced Safety Surveillance of Seasonal Quadrivalent Influenza Vaccines
           in English Primary Care: Interim Analysis
    • Authors: Simon de Lusignan; Gaël Dos Santos; Rachel Byford; Anne Schuind; Silvia Damaso; Vishvesh Shende; Chris McGee; Ivelina Yonova; Filipa Ferreira
      Abstract: Introduction The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced safety surveillance (ESS) of seasonal influenza vaccines including a near real-time evaluation of collected data. The objective was to identify whether the use of passive surveillance or active surveillance provides different results of reported adverse events of interest (AEIs) by specified age strata and AEI type. We report the weekly incidence rates of AEIs within 7 days following seasonal influenza vaccination using passive and active surveillance. Methods AEIs were collected within 7 days of vaccination from ten general practices predominantly administering inactivated quadrivalent influenza vaccine (IIV4, Fluarix Tetra, GSK). Vaccinees completed an adverse drug reaction (ADR) card. ADR card and medically attended AEIs data were recorded in practice electronic health records. We report the outcome of the first 5 weeks of safety surveillance (September 12, 2016–October 16, 2016); in an exploratory analysis, rates of AEI for IIV4 are compared to those passively reported through a sentinel network. Results Practices vaccinated 13.1% (12,864/98,091) of their registered population; 5.6% (95% CI 5.20–6.00) of them reported AEIs, none serious. The most frequent were respiratory 2.60% (95% CI 2.33–2.88), musculoskeletal 1.82% (95% CI 1.59–2.05) and neurological 1.05% (95% CI 0.88–1.23). AEIs were more frequently reported for adults than for children; 5.91% (95% CI 5.49–6.34) compared to 1.49% (95% CI 0.69–2.29); 47.18% of the adults reported AEI using the ADR card, none were returned for subjects < 18 years old. The frequency of AEIs reporting was higher, 6.88% (95% CI 6.35–7.42) vs. 3.30% (95% CI 2.68–3.96, 100/3028, p < 0.000), through ESS than passive surveillance. Conclusion The ESS did not reveal any safety signal and we demonstrated the feasibility of conducting ESS following EMA recommendations. The use of a customised ADR card led to a doubling of AEIs reports over passive surveillance in adults. Funding GlaxoSmithKline Biologicals SA, Wavre, Belgium.
      PubDate: 2018-07-11
      DOI: 10.1007/s12325-018-0747-4
  • Applying Reflective Multicriteria Decision Analysis (MCDA) to
           Patient–Clinician Shared Decision-Making on the Management of
           Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the Spanish
    • Authors: Monika Wagner; Dima Samaha; Jesus Cuervo; Harshila Patel; Marta Martinez; William M. O’Neil; Paula Jimenez-Fonseca
      Abstract: Introduction Unresectable, well-differentiated nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be monitored (watchful waiting, WW) or treated with systemic therapy such as somatostatin analogues (SSAs) to delay progression. We applied a reflective multicriteria decision analysis (MCDA) shared-decision framework (previously developed for the USA) to explore what matters to Spanish patients and clinicians considering GEP-NET treatment options. Methods The EVIDEM-derived framework was updated and adapted to the Spanish context. During a Chatham House session, five patients and six physicians assigned criteria weights using hierarchical point allocation and direct rating scale (alternative analysis). Informed by synthesized evidence embedded in the framework, participants scored how each criterion favored SSA treatment (reference case lanreotide) or WW and shared insights and knowledge. Weights and scores were combined into value contributions (norm. weight × score/5), which were added across criteria to derive the relative benefit–risk balance (RBRB, scale − 1 to + 1). Exploratory comparisons to US study findings were performed. Results Focusing on intervention outcomes (effectiveness, patient-reported, and safety), the mean RBRB favored treatment over WW (+ 0.32 ± 0.24), with the largest contributions from progression-free survival (+ 0.11 ± SD 0.07), fatal adverse events (+ 0.06 ± SD 0.08), and impact on HRQoL (+ 0.04 ± SD 0.04). Consideration of modulating criteria (type of benefit, need, costs, evidence, and feasibility) increased the RBRB to + 0.50 ± 0.14, with type of therapeutic benefit (+ 0.10 ± SD 0.08) and quality of evidence (+ 0.08 ± SD 0.06) contributing most towards treatment. Alternative weighting yielded similar results. Results were broadly comparable to those derived from the US study. Conclusion The multicriteria framework helped Spanish patients and clinicians identify and express what matters to them. The approach is transferable across decision-making contexts. Funding IPSEN Pharma.
      PubDate: 2018-07-09
      DOI: 10.1007/s12325-018-0745-6
  • Permacol™ Collagen Paste Injection in Anal Fistula Treatment: A
           Retrospective Study with One-Year Follow-Up
    • Authors: Mehmet Bayrak; Yasemin Altıntas
      Abstract: Introduction This study aimed to evaluate the applicability, safety, results, and functional performance of Permacol™ collagen paste injection in patients with an anal fistula. Methods Thirty-one patients with anal fistula underwent Permacol™ collagen paste injection between February 2015 and February 2017. The patients were followed up for a total of 12 months with recovery conditions monitored at intervals of 3, 6, and 12 months. Preoperative insertion of seton was performed in 15 patients for a period of 6–8 weeks and 2 patients for a period of 12 weeks. Results A trans-sphincteric anal fistula was present in 20 patients and an intersphincteric fistula was present in 11 patients. There was a recurrence in 7 patients (22.5%): 1 patient (3.2%) after 1-month follow-up, 3 patients (9.7%) after 3-month follow-up, 2 patients (6.5%) after 6-month follow-up, and 1 patient (3.2%) after 12-month follow-up. A complete recovery was observed in 24 (77.5%) patients after a 12-month follow-up. The mean Fecal Incontinence Severity Index score was 0.29 ± 0.64 preoperatively and 0.55 ± 1.03 after 12 months. Conclusion In this study, we show that treatment of patients with an anal fistula by injection of Permacol™ is a safe and successful method that does not compromise continence.
      PubDate: 2018-07-02
      DOI: 10.1007/s12325-018-0743-8
  • Pharmacokinetics and Safety of DS-8500a, an Antidiabetic Drug, in Japanese
           Subjects with Hepatic or Renal Impairment: A Single-Center, Open-Label,
           Single-Dose Study
    • Authors: Manabu Kato; Hitoshi Ishizuka; Takashi Taguchi; Kazuhito Shiosakai; Emi Kamiyama; Michio Sata; Takafumi Yoshida
      Abstract: Introduction The pharmacokinetics, safety, and tolerability of DS-8500a (a G protein receptor 119 agonist) up to 100 mg have been investigated in healthy Japanese adults. The objective of this study was to evaluate the effects of hepatic or renal impairment on the pharmacokinetics of a single 25-mg oral dose of DS-8500a. Methods This single-center, open-label study enrolled subjects into eight groups according to hepatic function (normal; mild or moderate impairment) and renal function [normal; mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]. Drug concentrations were measured by liquid-chromatography tandem mass spectrometry. Pharmacokinetic parameters were evaluated by non-compartmental analysis. Adverse events (AEs) were evaluated for safety. Results The hepatic and renal groups enrolled 15 and 30 subjects, respectively. Pharmacokinetic parameters of DS-8500a were comparable between the normal hepatic function and mild hepatic impairment groups, but the mean area under the concentration–time curve (AUC) was 1.37-fold higher, and the half-life was longer in the moderate hepatic impairment group compared with the normal hepatic function group. The maximum concentration (Cmax) and AUC values were 0.704- and 0.609-fold lower, respectively, in the ESRD group compared with the values in the other renal impairment groups; no clear differences in AUC and time to Cmax were observed in the normal function and mild, moderate, and severe renal impairment groups. There was no relationship between apparent total body clearance and estimated glomerular filtration rate. The incidence of AEs was similar among all groups. Conclusion DS-8500a exposure in the mild hepatic impairment and mild to severe renal impairment groups was similar to that in the corresponding normal hepatic and renal function groups, but dose adjustments may be required in those with moderate hepatic impairment and ESRD. Trial registration Japic CTI-No. 163135. Funding Daiichi Sankyo Co. Ltd., Tokyo, Japan.
      PubDate: 2018-07-02
      DOI: 10.1007/s12325-018-0739-4
  • Use of Nimesulide During Early Pregnancy and the Risk of Congenital
           Malformations: A Population-Based Study from Italy
    • Authors: Anna Cantarutti; Matteo Franchi; Federico Rea; Luca Merlino; Giovanni Corrao
      Abstract: Introduction Nimesulide is the most prescribed non-steroidal anti-inflammatory drug in Italy, and it is currently marketed in about 50 countries worldwide. The association between the use of nimesulide in early pregnancy and the risk of birth defects was investigated in a large cohort of pregnant women from Italy. Methods Data were from the healthcare utilization databases of the Italian region of Lombardy. The cohort of 353,081 newborns occurring in Lombardy during the period 2005–2010 was investigated. Exposure to nimesulide during the first trimester of pregnancy, and congenital malformations detected at presentation and within 90 days after birth (outcome), were investigated. Exposure–outcome association was measured by the ratio between the prevalence of congenital malformations among users and non-users of nimesulide. Propensity score stratification was used to control for potential confounders, including maternal medical comorbidities, concomitant medications and sociodemographic characteristics. Results The 627 (0.18%) women who filled prescriptions for nimesulide in the first trimester of pregnancy had a 2.6-fold risk of having children with congenital urinary tract anomalies compared to those who did not (adjusted prevalence ratio 2.6; 95% CI 1.2–5.7). Weaker and non-significant evidence for congenital malformations as a whole was found (adjusted prevalence ratio 1.2, 95% CI 0.9–1.6). Conclusion Our study suggests that the use of nimesulide in early pregnancy may result in a greater risk of having births with congenital urinary tract anomalies. Funding This study was funded by grants from the Italian Ministry of the Education, University and Research (’Fondo d’Ateneo per la Ricerca’ portion, year 2015).
      PubDate: 2018-06-19
      DOI: 10.1007/s12325-018-0735-8
  • New Method for Insomnia Mongolian Mind–Body Interactive Psychotherapy in
           the Assessment of Chronic Insomnia: A Retrospective Study
    • Authors: Nagongbilige He; Wu Lan; Aruna Jiang; Haserden Jia; Shuzhi Bao; Longmei Bao; Altansha Qin; Orgel Bao; Shinjiltu Bao; Nandin Wang; Suyaltu Bao; Shuangfu Dai; Sarula Bao; Sarnai Arlud
      Abstract: Introduction Insomnia is a common clinical complaint, and if not addressed it can increase the risk of developing other underlying diseases such as hypertension, depression and anxiety. The use of Mongolian mind–body interactive therapy as a comprehensive psychotherapeutic approach in chronic insomnia has been shown in this retrospective study. Methods Subjects who had suffered insomnia for more than 1 month participated in the Mongolian mind–body interactive psychotherapy program between June 2012 and February 2014. They were interviewed by telephone at least 10 months before participating in the program. Their sleep was assessed using the Athens insomnia scale. Descriptive statistics, ANOVA and regression analysis were used for data analysis by SPSS software. Results Mongolian mind–body interactive psychotherapy significantly improved sleeping conditions. In ANOVA analysis, both short- and long-term outcomes were significantly affected by the treatment period. Patients who previously took medication and pre-treatment sleeping condition (ASI score) had a significant influence on long-term outcomes, as well as treatment time related to the duration of insomnia. Conclusion Mongolian mind–body interactive psychotherapy is a new method for insomnia, and narrative therapy and hypnotic methods together improve the sleeping condition, However, a further controlled randomized clinical study is needed to understand the efficacy.
      PubDate: 2018-06-19
      DOI: 10.1007/s12325-018-0726-9
  • Assessment of Relationship of Serum Neurokinin-B Level in the
           Pathophysiology of Pre-eclampsia: A Case–Control Study
    • Authors: Henna Salman; Mohsin Shah; Asif Ali; Asma Aziz; Salvatore Giovanni Vitale
      Abstract: Introduction Pre-eclampsia is a pregnancy-induced disorder that complicates approximately 5–7% of pregnancies. It is the leading cause of maternal and foetal morbidity and mortality worldwide. Aim To determine the role of serum neurokinin-B level in the pathophysiology of pre-eclampsia. Methods This was a case–control study. A total of 80 pregnant women in their third trimester of pregnancy were included in the study. They were divided into two groups (40 pre-eclamptic and 40 normotensive) according to the presence or absence of clinical parameters of pre-eclampsia. Serum level of neurokinin-B was measured with ELISA. Results Maternal age, weight, BMI, pulse, systolic BP and diastolic BP were statistically higher in the pre-eclampsia group compared to the normotensive group (P < 0.0001). Moreover, statistically higher levels were observed for neurokinin-B in the normotensive group as compared to the pre-eclamptic group. The mean value of neurokinin-B was 83.50 ng/L in the pre-eclamptic group compared to 111.5 ng/L in the normotensive group (P = 0.006). Conclusion Higher levels of serum neurokinin-B were observed in the normotensive pregnant females as compared to the pre-eclamptic females. Thus, apparently, it seems that serum neurokinin-B plays no role in the pathophysiology of pre-eclampsia, and further large multicentre prospective studies may be required to ascertain its role.
      PubDate: 2018-06-19
      DOI: 10.1007/s12325-018-0723-z
  • Current Treatment of Endolymphatic Sac Tumor of the Temporal Bone
    • Authors: William M. Mendenhall; Carlos Suárez; Alena Skálová; Primož Strojan; Asterios Triantafyllou; Kenneth O. Devaney; Michelle D. Williams; Alessandra Rinaldo; Alfio Ferlito
      Abstract: An endolymphatic sac tumor (ELST) is a rare, indolent but locally aggressive tumor arising in the posterior petrous ridge. Patients present with sensorineural hearing loss and tinnitus. As the tumor progresses, patients may experience vertigo, ataxia, facial nerve paresis, pain and otorrhea. Most patients present in their 4th or 5th decade with a wide age range. Patients with von Hippel–Lindau disease have an increased likelihood of developing ELST. Histologically, ELST is a low-grade adenocarcinoma. As it progresses, it destroys bone and extends into adjacent tissues. The likelihood of regional or distant metastases is remote. The optimal treatment is resection with negative margins. Patients with positive margins, gross residual disease, or unresectable tumor are treated with radiotherapy or radiosurgery. Late recurrences are common, so long follow-up is necessary to assess efficacy. The likelihood of cure depends on tumor extent and is probably in the range of 50–75%.
      PubDate: 2018-06-19
      DOI: 10.1007/s12325-018-0730-0
  • The Impact of Adding a Training Device to Familiar Counselling on
           Inhalation Technique and Pulmonary Function of Asthmatics
    • Authors: Mina Nicola; Ahmed Elberry; Ossama Sayed; Raghda Hussein; Haitham Saeed; Mohamed Abdelrahim
      Abstract: Introduction We have investigated the effect of adding a pressurized metered dose inhaler (pMDI) training device to verbal counselling on pulmonary function and inhalation technique. Methods A total of 304 adult asthmatic subjects (> 18 years old) were enrolled in a 3-month study of assessment and education. They were divided into an investigation group (Trainhaler plus Flo-Tone and verbal counselling, n = 261, mean age 49.2 years) and a control group (verbal counselling only, n = 43, mean age 48.7 years). Pulmonary function and inhalation technique were evaluated, mistakes noted, and the correct technique advised at three consecutive monthly visits. Visits also included verbal pMDI counselling (both groups) and training device coaching (investigation group). Results By visit 2, the mean number of technique errors decreased significantly (p < 0.05) in both groups (investigation group p < 0.001). The investigation group demonstrated a marked decrease in the frequency of the critical error of maintaining a slow inhalation rate until the lungs are full—a technique difficult to learn via verbal counselling alone. The improvement in pulmonary function was significant from the second clinic visit in the investigation group (p < 0.05) and from the third visit in both groups (p < 0.001). Conclusions Use of a training device combined with verbal counselling improved inhalation technique. An earlier, significant improvement was also noted in pulmonary function.
      PubDate: 2018-06-15
      DOI: 10.1007/s12325-018-0737-6
  • Administration of Micronized Purified Flavonoid Fraction During
           Sclerotherapy of Reticular Veins and Telangiectasias: Results of the
           National, Multicenter, Observational Program VEIN ACT PROLONGED-C1
    • Authors: Vadim Y. Bogachev; Boris V. Boldin; Pavel Y. Turkin
      Abstract: Introduction Sclerotherapy is a common technique for the removal of intradermal veins. This study examined the rationale for prescribing micronized purified flavonoid fraction (MPFF) in clinical, etiological, anatomic, pathophysiologic (CEAP) class C1 patients with dilated intradermal veins scheduled for sclerotherapy. Methods In a national, multicenter, observational program, physicians recruited CEAP C1s patients scheduled for sclerotherapy. The decision to prescribe adjuvant MPFF (1000 mg/day for 6 weeks beginning 2 weeks before sclerotherapy) was made according to usual practice. Disease severity and treatment outcomes were assessed at baseline and 4 weeks post-sclerotherapy using a visual analog scale (VAS) as well as quality-of-life (CIVIQ-14) and patient satisfaction (Darvall) questionnaires. Results A total of 70 physicians recruited 1150 patients: 1071 (93%) women, 79 (7%) men. Mean age (± SD) was 40.7 ± 10.7 years (range 18–74) and mean body mass index was 23.6 ± 3.3 kg/m2. Reticular veins were observed in 42.1% of patients and 57.9% had telangiectasias. MPPF was prescribed to 905 patients (79%). Sclerotherapy was associated with statistically significant decreases in mean VAS scores for leg heaviness, pain, sensation of swelling, night cramps, and itching. For each symptom, MPFF-treated patients showed a more pronounced improvement than those undergoing sclerotherapy alone: mean VAS pain score with MPFF decreased from 1.90 ± 2.30 to 0.30 ± 0.62 versus 1.72 ± 1.93 to 0.52 ± 0.99 with sclerotherapy alone; mean VAS leg heaviness score with MPFF decreased from 2.80 ± 2.43 to 0.47 ± 1.07 versus 2.38 ± 2.23 to 0.76 ± 0.85 with sclerotherapy alone. Patient quality-of-life indicators improved with symptom resolution, particularly pain, and for each indicator the observed improvement was greater with MPFF. The outcomes of treatment exceeded patient expectations. Fewer patients experienced sclerotherapy-induced hyperpigmentation with adjunctive MPFF versus sclerotherapy alone (33.9% versus 41.2%, respectively, P = 0.034). No adverse events related to MPFF were observed. Conclusion Resolution of venous symptoms post-sclerotherapy was greater in patients treated with MPFF compared with those undergoing sclerotherapy alone, supporting the rationale for use of MPFF in patients undergoing sclerotherapy. Funding Servier.
      PubDate: 2018-06-15
      DOI: 10.1007/s12325-018-0731-z
  • Unlicensed and Off-Label Medication Use in Pediatric and Neonatal
           Intensive Care Units: No Change Over a Decade
    • Authors: Hadar Nir-Neuman; Ibrahim Abu-Kishk; Michal Toledano; Eli Heyman; Tomer Ziv-Baran; Matitiahu Berkovitch
      Abstract: Introduction Many of the medications prescribed to children are off-label and/or unlicensed because pharmacologic evaluations have not been performed in this age group. Methods All drugs prescribed to patients admitted to the neonatal intensive care units (NICU) (n = 134) and pediatric intensive care units (PICU) (n = 56) during a 2-month observation period were recorded and classified according to patient age, drug license status, indicated use, and typical dosing, frequency and way of administration. Results were compared with prior data collected in 2002, from the same units. Results In the NICU, among the 1064 prescriptions for 49 medications, 312 (29.2%) were licensed and 63 (5.9%) unlicensed, and 693 (64.8%) were off-label use. For the neonates, 23.9% and 96.3% received at least one unlicensed medication and one off-label medication, respectively. While the difference in off-label use between the two time periods was not statistically significant, unlicensed medications were less frequently prescribed in 2016 (5.9 versus 16.6%, p = 0.001). Regarding the PICU, among the 388 prescriptions for 75 medications, 205 (52%) were licensed and 13 (3.4%) unlicensed, and 170 (43.8%) were off-label. In contrast, in 2002, none of the medications prescribed were unlicensed (p = 0.001). The number of off-label medications (41%) and number of PICU patients receiving at least one unlicensed/off-label medication in these two time periods (88.7% versus 90.5% for 2016 and 2002, respectively) were similar. Conclusions The current study confirms the high prevalence of unlicensed and off-label drug use in a PICU and NICU setting. Compared with a similar study conducted in the same PICU in 2002, despite regulatory efforts conducted in this area, the prevalence of unlicensed medications was surprisingly higher.
      PubDate: 2018-06-15
      DOI: 10.1007/s12325-018-0732-y
  • Rapid and Consistent Improvements in Morning PEF in Patients with Severe
           Eosinophilic Asthma Treated with Mepolizumab
    • Authors: Hector Ortega; Andrew Menzies-Gow; Jean-Pierre Llanos; Mark Forshag; Frank Albers; Necdet Gunsoy; Eric S. Bradford; Steven W. Yancey; Monica Kraft
      Abstract: Introduction Previous studies showed that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. However, early studies reported inconsistent effects on lung function. This study specifically assessed the onset of clinical effect and the relationship of baseline blood eosinophil count of mepolizumab 100 mg subcutaneous (SC) administration on morning peak expiratory flow (AM PEF). Methods Post hoc analysis of data from two randomized, double-blind, placebo-controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma. Individual study results were generated using a mixed model repeated measures model controlling for multiple covariates and were combined using a fixed effects meta-analysis via inverse-variance weighting. Results Significant improvements in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as early as week 1 and continued to improve further with subsequent doses. The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p < 0.001. When the population was stratified by blood eosinophil thresholds the mean difference from placebo was 24 L/min (≥ 150 cells/µL), 27 L/min (≥ 300 cells/µL), and 34 L/min (≥ 500 cells/µL), p < 0.001 for all subgroups. The < 150 cells/µL (≥ 300 cells/µL in the previous year) group increased 13 L/min, while both 150 to < 300 cells/µL and 300 to < 500 cells/µL ranges demonstrated comparable changes (19 L/min and 17 L/min), respectively. Conclusion Our analysis has shown early and consistent improvements in lung function measured by AM PEF using the study enrollment criterion of ≥ 150 eosinophils/µL. We also identified a relationship between baseline blood eosinophils and improvements in AM PEF with mepolizumab in patients with severe eosinophilic asthma. Funding GlaxoSmithKline (study ID 208091).
      PubDate: 2018-06-15
      DOI: 10.1007/s12325-018-0727-8
  • Safety and Tolerability of Combinations of Empagliflozin and Linagliptin
           in Patients with Type 2 Diabetes: Pooled Data from Two Randomized
           Controlled Trials
    • Authors: Ralph A. DeFronzo; Christopher Lee; Sven Kohler
      Abstract: Introduction Two 52-week Phase III studies evaluated the efficacy and safety of once-daily combinations of empagliflozin/linagliptin as monotherapy or add-on to metformin in patients with type 2 diabetes (T2DM). The aim of this analysis was to further assess the safety and tolerability of empagliflozin/linagliptin compared with their individual components in patients with T2DM, using pooled data from these trials. Methods A total of 1363 patients were treated with empagliflozin 25 mg/linagliptin 5 mg (n = 273), empagliflozin 10 mg/linagliptin 5 mg (n = 272), empagliflozin 25 mg (n = 276), empagliflozin 10 mg (n = 275), or linagliptin 5 mg (n = 267). Adverse events (AEs) were assessed descriptively in patients who took ≥ 1 dose of study drug. Results Total exposure was 251, 255, 256, 249, and 243 patient-years in the empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg groups, respectively. The proportion of patients with ≥ 1 AE was similar across groups (70.4–74.9%). The percentage of patients with confirmed hypoglycemic AEs (plasma glucose ≤ 70 mg/dL and/or requiring assistance) was low in all groups (1.1–2.2%); none required assistance. Events consistent with urinary tract infection were reported in similar percentages of patients in all groups (11.4–13.8%), and in a greater proportion of female than male patients. Events consistent with genital infection were reported in higher percentages of patients on empagliflozin/linagliptin or empagliflozin (4.0–6.5%) than linagliptin 5 mg (2.6%), and in a greater proportion of females than males. The risks of hypersensitivity reactions and events consistent with volume depletion were low across treatment groups. Conclusion Empagliflozin/linagliptin as monotherapy or add-on to metformin for 52 weeks was well tolerated in patients with T2DM, with safety profiles similar to individual components, including a low risk of hypoglycemia. Funding The Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Trial Registration identifiers, NCT01422876 & NCT01422876.
      PubDate: 2018-06-15
      DOI: 10.1007/s12325-018-0724-y
  • Efficacy of Phonosurgery, Logopedic Voice Treatment and Vocal Pedagogy in
           Common Voice Problems of Singers
    • Authors: Maria del Mar Ropero Rendón; Tatiana Ermakova; Marie-Louise Freymann; Alina Ruschin; Tadeus Nawka; Philipp P. Caffier
      Abstract: Introduction Functional and organic impairments of the singing voice are common career-threatening problems of singers presenting in phoniatric and laryngological departments. The objective was to evaluate the efficacy of phonosurgery, logopedic voice treatment and vocal pedagogy in common organic and functional voice problems of singers, including investigation of the recently introduced parameter vocal extent measure (VEM). Methods In a prospective clinical study, the analysis of treatment outcome in 76 singers [57 female, 19 male; 38 ± 11 years (mean ± SD)] was based on pre- and post-therapeutic voice function diagnostics and videolaryngostroboscopy. Examination instruments included auditory-perceptual voice assessment, voice range profile (VRP), the VEM calculated from area and shape of the VRP, acoustic–aerodynamic analysis, and patients’ self-assessment (e.g., Singing Voice Handicap Index). Results While 28% of all singers (21/76) presented with functional dysphonia, 72% (55/76) were diagnosed with organic vocal fold changes, of which marginal edema (n = 25), nodules (n = 9), and polyps (n = 8) were the most common pathologic changes. Of the 76 singers, 57% (43) received phonosurgery, 43% (33) had conservative pedagogic (14) and logopedic (19) treatment. Three months post-therapeutically, most parameters had significantly improved. The dysphonia severity index (DSI) increased on average from 6.1 ± 2.0 to 7.4 ± 1.8 (p < 0.001), and the VEM from 113 ± 20 to 124 ± 14 (p < 0.001). Both parameters correlated significantly with each other (rs = 0.41). Phonosurgery had the largest impact on the improvement of vocal function. Conservative therapies provided smaller quantitative enhancements but also qualitative vocal restoration with recovered artistic capabilities. Conclusions Depending on individual medical indication, phonosurgery, logopedic treatment and voice teaching are all effective, objectively and subjectively satisfactory therapies to improve the impaired singing voice. The use of VEM in singers with functional and organic dysphonia objectifies and quantifies their vocal capacity as documented in the VRP. Complementing the established DSI, VEM introduction into practical objective voice diagnostics is appropriate and desirable especially for the treatment of singers.
      PubDate: 2018-06-15
      DOI: 10.1007/s12325-018-0725-x
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