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Publisher: Springer-Verlag (Total: 2573 journals)

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Showing 1 - 200 of 2573 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 4)
3D Research     Hybrid Journal   (Followers: 21, SJR: 0.222, CiteScore: 1)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 11, SJR: 0.825, CiteScore: 1)
AAPS J.     Hybrid Journal   (Followers: 29, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 8, SJR: 0.752, CiteScore: 3)
Abdominal Radiology     Hybrid Journal   (Followers: 18, 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: 30, SJR: 0.53, CiteScore: 1)
Academic Questions     Hybrid Journal   (Followers: 9, SJR: 0.106, CiteScore: 0)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 31, SJR: 0.316, CiteScore: 1)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.359, CiteScore: 1)
Acoustics Australia     Hybrid Journal   (Followers: 1, 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: 19, 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: 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: 24, 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: 4, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 19, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
Adaptive Human Behavior and Physiology     Hybrid Journal  
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8, SJR: 0.103, CiteScore: 0)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 28, 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: 19, SJR: 1.005, CiteScore: 2)
Adolescent Research Review     Hybrid Journal   (Followers: 1)
Adsorption     Hybrid Journal   (Followers: 5, SJR: 0.703, CiteScore: 2)
Advanced Composites and Hybrid Materials     Hybrid Journal  
Advanced Fiber Materials     Full-text available via subscription  
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.698, CiteScore: 1)
Advances in Astronautics Science and Technology     Hybrid Journal  
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 40, SJR: 0.956, CiteScore: 2)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 21, SJR: 0.812, CiteScore: 1)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 58, 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: 35, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.475, CiteScore: 2)
Advances in Neurodevelopmental Disorders     Hybrid Journal  
Advances in Polymer Science     Hybrid Journal   (Followers: 49, 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: 4, SJR: 0.673, CiteScore: 2)
Aerosol Science and Engineering     Hybrid Journal  
Aerospace Systems     Hybrid Journal   (Followers: 1)
Aerotecnica Missili & Spazio : J. of Aerospace Science, Technologies & Systems     Hybrid Journal  
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)
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: 7, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Open Access   (Followers: 15, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Open Access   (Followers: 20, SJR: 0.663, CiteScore: 1)
Agronomy for Sustainable Development     Open Access   (Followers: 15, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 9, SJR: 0.227, CiteScore: 1)
AIDS and Behavior     Hybrid Journal   (Followers: 16, 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: 7, 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: 2)
AMBIO     Hybrid Journal   (Followers: 10, SJR: 1.569, CiteScore: 4)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 17, 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: 6, SJR: 0.181, CiteScore: 0)
American J. of Potato Research     Hybrid Journal   (Followers: 3, SJR: 0.611, CiteScore: 1)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 22, SJR: 0.314, CiteScore: 0)
American Sociologist     Hybrid Journal   (Followers: 16, SJR: 0.35, CiteScore: 0)
Amino Acids     Hybrid Journal   (Followers: 7, SJR: 1.135, CiteScore: 3)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 10, SJR: 0.211, CiteScore: 1)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 6, 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: 23, 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: 19, SJR: 1.042, CiteScore: 3)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.932, CiteScore: 1)
Annals of Data Science     Hybrid Journal   (Followers: 13)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.85, CiteScore: 2)
Annals of Finance     Hybrid Journal   (Followers: 35, 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: 13, SJR: 0.413, CiteScore: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 13, 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: 11, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 13)
Annals of PDE     Hybrid Journal  
Annals of Regional Science     Hybrid Journal   (Followers: 9, SJR: 0.614, CiteScore: 1)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 11, 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: 3, SJR: 0.294, CiteScore: 1)
Applications of Mathematics     Hybrid Journal   (Followers: 3, 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: 19, SJR: 0.21, CiteScore: 1)
Applied Categorical Structures     Hybrid Journal   (Followers: 4, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 53, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 7, 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: 15, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 10, SJR: 0.886, CiteScore: 1)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (Followers: 1, 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: 68, 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: 26, 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: 6, 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: 3, 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: 22, SJR: 1.052, CiteScore: 2)
Archaeologies     Hybrid Journal   (Followers: 13, SJR: 0.224, CiteScore: 0)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.725, CiteScore: 1)
Archival Science     Hybrid Journal   (Followers: 68, 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: 171, 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: 18, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 10, 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: 11, SJR: 1.493, CiteScore: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 18, 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: 17, 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: 3, SJR: 0.2, CiteScore: 0)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.766, CiteScore: 1)
arktos : The J. of Arctic Geosciences     Hybrid Journal  
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: 12, SJR: 0.937, CiteScore: 2)
Artificial Intelligence Review     Hybrid Journal   (Followers: 22, SJR: 0.833, CiteScore: 4)
Artificial Life and Robotics     Hybrid Journal   (Followers: 10, SJR: 0.226, CiteScore: 0)
Asia Europe J.     Hybrid Journal   (Followers: 4, 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: 17, SJR: 1.185, CiteScore: 2)

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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  [2573 journals]
  • Paraneoplastic Syndromes Associated with Laryngeal Cancer
    • Abstract: Objectives Paraneoplastic syndromes occur rarely in association with laryngeal cancer. When present, the syndrome may be the first sign of the malignancy. The aim of the present study was to review and report on all published cases in the international literature. Methods A search of PubMed was conducted for “paraneoplastic syndromes in laryngeal cancer” without any restrictions on language or publication year. The full texts of all relevant articles were reviewed and all cases of paraneoplastic syndromes associated with any type of laryngeal cancer were extracted and analyzed. Results We identified 59 cases of paraneoplastic syndromes related to laryngeal cancer in the literature published from 1963 until recently. There were 46 squamous cell carcinomas and 10 neuroendocrine carcinomas. Twenty-two of the paraneoplastic syndromes involved the endocrine system, 21 were dermatologic or cutaneous, 8 neurologic, 5 osteoarticular or rheumatologic, 1 ocular, 1 muscular, and 1 hematologic. Treatment strategies included surgery, radiotherapy, chemotherapy, and often multimodal therapy, depending on the histology and stage of the laryngeal cancer. Conclusions Because of their rarity, paraneoplastic syndromes associated with laryngeal cancer are difficult to diagnose. By presenting and systematically reviewing all published cases in the international literature, the present review may help clinicians to recognize them and to suspect the diagnosis of laryngeal cancer at an earlier stage than otherwise might be possible.
      PubDate: 2019-12-04
  • Validation of Waste Anaesthetic Gas Exposure Limits When Using a Closed
           Vaporizer Filling System: A Laboratory-Based Study
    • Abstract: Introduction It is desirable to minimise exposure of personnel to halogenated inhaled anaesthetics in the operating room to avoid deleterious short-term and long-term health effects. The objective of this study was to determine whether, while filling anaesthetic vaporizers with sevoflurane using AbbVie’s closed vaporizer filling system (Quik-Fil™), concentrations of sevoflurane in ambient air remained at or below recommended levels when measured at different operator heights. Methods Nine filling runs were conducted, with measurement heights of 95, 130, 140, 150, 160, and 185 cm. Within each 15-min run, five vaporizers were sequentially filled from bottles of sevoflurane with the closed valving system. Ambient-air sevoflurane concentration in the breathing zone was continuously measured once per second by using a MIRAN SapphIRe 205BXL portable ambient air analyser. Results The use of the closed filling system maintained a level of waste anaesthetic gas exposure that was well below (mean, 0.10 ppm; maximum, 0.16 ppm) the recommended short-term value of 20 ppm average for 15 min provided by the Swedish Work Environment Authority and also fell below the US limit of a time-weighted average of 2 ppm provided by the National Institute for Occupational Safety and Health. Exposure to sevoflurane appeared to be independent of the height at which the measurement was made. Conclusions The presence of sevoflurane in the work environment while using the closed filling system maintains a level of waste anaesthetic gas exposure well below the recommended levels at all tested operator heights.
      PubDate: 2019-12-04
  • Cost-Effectiveness of Reimbursing Infliximab for Moderate to Severe
           Crohn’s Disease in China
    • Abstract: Objectives To assess the cost-effectiveness of reimbursing infliximab for moderate-to-severe Crohn’s disease (MS-CD) in China from the perspective of public insurance payers. Methods A decision-analytic model with a lifetime time horizon was constructed to simulate the disease progression and direct medical costs in Chinese MS-CD patients under two scenarios: reimbursing infliximab vs. not reimbursing infliximab. A cross-sectional study and literature review were conducted to estimate model variables. The constructed decision-analytic model ran the base case, one-way sensitivity, and probabilistic sensitivity analyses (PSA) to assess the cost-effectiveness of reimbursing infliximab using reimbursed medical costs. Results Base case analysis discounting health benefits and costs estimated that reimbursing infliximab could increase overall survival by 0.604 years, increase total quality-adjusted life years (QALY) by 0.697 QALY, reduce absolute lifetime surgery risk by 13.1%, and increase reimbursed costs by ¥29,409. The incremental cost-effectiveness ratio per gained additional QALY (ICER) based on discounted health benefits and reimbursed medical costs (3% per year) was ¥42,198. The one-way sensitivity analyses identified that the cost-effectiveness of reimbursing infliximab for MS-CD was mainly driven by the treatment efficacies of maintenance therapy, quality of life, and unit price of infliximab. PSA estimated that reimbursing infliximab was associated with a 63.8% chance to be cost-effective under the willingness-to-pay of the 2018 Chinese gross domestic product per capita (GDPPC). Conclusion Reimbursing infliximab for MS-CD in Chinese patients was highly attractive, costing Chinese public insurance payers less than the 2018 Chinese GDPPC to gain 1 QALY.
      PubDate: 2019-12-03
  • Adhesion Evaluation of AG200-15: An Investigational Transdermal
           Contraceptive Delivery System
    • Abstract: Introduction AG200-15, an investigational transdermal contraceptive delivery system or patch, is designed to be a low-dose, non-daily, combined hormonal contraceptive option for women. In this phase 1 study, the in vivo adhesion of the AG200-15 patch was compared to Xulane®, the only contraceptive patch available in the USA. Methods This phase 1, randomized, open-label, single-dose, two-treatment, two-period crossover adhesion study compared the 7-day adhesion of the AG200-15 and Xulane contraceptive patches. Eighty-three women, ages 18 to 35 years old, with body mass index (BMI) ≥ 19 kg/m2 and < 35 kg/m2, and weight ≥ 48 kg and < 90 kg were enrolled. Trained study site personnel used a five-point scale to assess patch adhesion daily. A score of 0 reflected at least 90% adhesion; while a score of 4 represented complete detachment of the patch. The primary objective was to compare the adhesion properties of the two patches; AG200-15 would be considered statistically non-inferior to Xulane if the upper 95% confidence limit (CL) of the mean difference in adhesion scores was below + 0.15. Results The overall mean (standard deviation) scores for AG200-15 (N = 78) and Xulane (N = 77) were 0.14 (0.28) and 0.39 (0.40), respectively (lower scores on the adhesion scale indicate better adhesion). The study demonstrated a difference in mean adhesion scores of − 0.24, meeting the prespecified non-inferiority criterion by demonstrating a one-sided upper CL of − 0.16. Thus, the in vivo adhesion of AG200-15 was shown to be non-inferior to that of Xulane. Most subjects experienced no skin irritation at the application site for either patch and no serious adverse event was reported in the study. Conclusion The in vivo adhesion of AG200-15 is non-inferior to that of Xulane on the basis of the prespecified criterion of the upper bound of the one-sided 95% CL for the mean adhesion score difference being below + 0.15. Both patches were generally well tolerated. Funding Agile Therapeutics, Inc.
      PubDate: 2019-12-01
  • Case Series of Combined XEN Implantation and Phacoemulsification in
           Chinese Eyes: One-Year Outcomes
    • Abstract: Purpose The outcome of XEN implantation in Chinese eyes has not been previously reported. The purpose of our study is to evaluate the efficacy and safety of combined cataract surgery and XEN implantation in Chinese eyes with glaucoma. Methods We conducted a prospective study of 31 consecutive Chinese patients who underwent combined phacoemulsification and XEN implantation at the National University Hospital (Singapore) in this study. Patients were assessed preoperatively and postoperatively on days 1 and 7, and months 1, 3, 6, and 12. The intraocular pressure (IOP), glaucoma medication use, Snellen visual acuity (VA), and complications were assessed at each visit. The Wilcoxon signed rank test for non-parametric data was used for the analysis of IOP and glaucoma medications at baseline versus 12 months after the procedure. Results The mean age of the patients was 70 ± 7.9 years and 48.4% were male. Twelve patients (38.7%) were diagnosed with primary open angle glaucoma and 19 patients (61.3%) were diagnosed with primary angle closure glaucoma. There was a significant decrease in IOP at 12 months (12.1 ± 2.6 mmHg) compared with preoperative medicated (15.6 ± 2.7 mmHg, p < 0.0001) and unmedicated IOP (22.1 ± 3.6 mmHg, p < 0.001). as well as a significant reduction in the number of glaucoma medications (1.4 ± 0.6 vs 0.1 ± 0.4, p < 0.0001). The most common complications were transient hypotony (12.9%) and ptosis (12.9%) and there were no sight-threatening intraoperative or postoperative complications. One patient required additional glaucoma surgery for uncontrolled IOP at 8 months after combined phacoemulsification and XEN implantation. Conclusion Combined XEN implantation with cataract surgery was effective in lowering the IOP and the number of glaucoma medications in Chinese eyes for at least 12 months, with a favorable safety profile.
      PubDate: 2019-12-01
  • The Symptoms and Impact of Recurrent Focal Segmental Glomerulosclerosis in
           Kidney Transplant Recipients: A Conceptual Model of the Patient Experience
    • Abstract: Introduction We qualitatively examined the symptoms and impact of recurrent primary focal segmental glomerulosclerosis (rpFSGS) in kidney transplant recipients, compared with two related FSGS populations, to characterize the experience of patients with rpFSGS. Methods A literature review identified 58 articles concerning the experience of patients with pFSGS and/or rpFSGS in three groups: pre-transplant pFSGS, post-transplant rpFSGS, or post-transplant non-recurrent pFSGS. Literature findings were used to construct a preliminary conceptual model incorporating the symptoms and impact of rpFSGS, which was refined on the basis of qualitative interviews with clinicians. Twenty-five patients (rpFSGS: n = 15; pre-transplant pFSGS: n = 5; post-transplant non-recurrent pFSGS: n = 5) were interviewed to characterize the experience of patients with rpFSGS and compare it with other FSGS populations, and findings were used to finalize the conceptual model. Results The impact of pFSGS/rpFSGS described in the literature was diverse. Treatment-related symptoms, along with anxiety and depression, were considered important features of rpFSGS in addition to the findings from the literature review, according to clinicians. Patient-reported tiredness and swelling were the most common/disturbing symptoms associated with rpFSGS, while physical activity restrictions and adverse effects on work/social life were considered the most profound impact concepts. The collective disease experience was different for patients with rpFSGS and non-recurrent pFSGS, although psychological impact, including treatment-related anxiety and depression, were common to both groups. Conclusions Post-transplant recipients with rpFSGS display a greater symptom burden and experience a more diverse impact than those with non-recurrent pFSGS, highlighting the importance of effective patient monitoring and introducing effective treatments for the prevention and management of pFSGS recurrence. Funding Astellas Pharma Global Development, Inc.
      PubDate: 2019-12-01
  • Comparison of PARPis with Angiogenesis Inhibitors and Chemotherapy for
           Maintenance in Ovarian Cancer: A Network Meta-Analysis
    • Abstract: Introduction Seventy-five percent of ovarian cancer would relapse within 18–28 months after platinum-base chemotherapy. Evidence suggests that maintenance chemotherapy is effective in prolonging remission. Recent target therapies such as poly(ADP-ribose) polymerase inhibitors (PARPis) and angiogenesis inhibitors (AIs) are known to ease burden and recurrence of ovarian cancer. There is limited data for head-to-head comparison of PARPis, AIs, and chemotherapeutic agents (CTAs) as maintenance treatment. This network meta-analysis thus assessed the effectiveness and toxicity of these three maintenance therapies in patients with ovarian cancer. Methods We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials assessing efficacy and safety of maintenance therapy in patients with ovarian cancer. Primary outcome was progression-free survival (PFS) as assessed by blinded review; safety and tolerability were secondary outcomes. A network meta-analysis to compare three drug classes was performed using statistical software R. Results We included 24 trials (11,366 patients) assessing efficacy and safety of PARPis (n = 4), AIs (n = 12), and CTAs (n = 8). PARPis [hazard ratio (HR) 0.64; 95% credible intervals (CrI) 0.55–0.73] and AIs (HR 0.87; 95% CrI 0.81–0.93) showed significant improvement in PFS compared to placebo but not CTA (HR 1.00; 95% CrI 0.86–1.15). PARPis showed significant improvement in PFS compared to AIs (HR 0.73; 95% CrI 0.63–0.86) and CTA (HR 0.64; 95% CrI 0.52–0.78). Adverse events (AEs) leading to treatment discontinuation and dose reduction were lower in PARPis [incidence rate ratio (IRR) 0.60; CrI 0.31–1.18 and IRR 0.73, 95% CrI 0.50–1.06, respectively] compared to AIs, but the differences were not significant. Conclusion PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of implications caused by AEs when compared to AIs. This network meta-analysis provides valuable evidence and significant insights into treatment of ovarian cancer.
      PubDate: 2019-12-01
  • Leber’s Hereditary Optic Neuropathy as a Promising Disease for Gene
           Therapy Development
    • Abstract: Abstract Leber’s hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy due to retinal ganglion cell (RGC) loss. It is a maternally inherited (or sporadic) mitochondrial disorder caused primarily by mutations in genes that encode components of respiratory complex (RC)1 in mitochondria. Mitochondrial deficiency of RC1 compromises ATP production and oxidative stress management in RGCs. The most common LHON-causing mutations are 11778G>A, 3460G>A, and 14484T>C point mutations in MT-ND4, MT-ND1, and MT-ND6. The unusually high mitochondrial load of RGCs makes them particularly sensitive to these mutations. Patients with LHON may be prescribed ubiquinone (a component of RC3) or idebenone, a ubiquinone analogue with enhanced bioavailability to act downstream of RC1. The challenge of accessing the inner mitochondrial membrane with gene therapy for LHON, and other mitochondrial diseases, may be overcome by incorporation of a specific mitochondrion-targeting sequence (MTS) that enables allotropic expression of a nucleus-transcribed ND4 transgene. Because LHON penetrance is incomplete among carriers of the aforementioned mutations, identification of environmental factors, such as heavy smoking, that interact with genetics in the phenotypic expression of LHON may be helpful toward preventing or delaying disease development. LHON has become a model for mitochondrial and neurogenerative diseases owing to it having a clearly identified genetic cause and its early onset and rapid progression characteristics. Hence, LHON studies and genetic treatment advances may inform research of other diseases.
      PubDate: 2019-12-01
  • Tocilizumab Effects on Coagulation Factor XIII in Patients with Rheumatoid
    • Abstract: Introduction Rheumatoid arthritis (RA) is a chronic systemic auto-immune disease associated with a prothrombotic state. Tocilizumab, an interleukin-6 receptor inhibitor, is highly effective in controlling disease activity and thrombotic risk. Factor XIII (FXIII), involved in thrombotic complications, has been reported to be reduced in RA patients during maintenance treatment with tocilizumab, but no data are available before and after the drug administration. Thus, we investigated the effects of tocilizumab on FXIII, thrombin generation and inflammation in patients with RA naïve for the drug. Methods We studied 15 consecutive adult patients with RA at baseline and 4 weeks after the onset of parenteral administration of tocilizumab, measuring disease activity and plasma levels of C-reactive protein (CRP), FXIII, and prothrombin fragments F1+2 by immunoenzymatic methods. Fifteen healthy subjects, sex-and age-matched with patients, served as normal controls for laboratory measurements. Results At baseline, patients with established RA had a median DAS28 of 4.8 (3.2–8.3) and, compared to healthy controls, had higher plasma levels of CRP (p < 0.0001), FXIII (p = 0.017) and F1+2 (p < 0.0001). Four weeks after starting treatment with tocilizumab, based on the EULAR response criteria, eight patients were classifiable as responders and seven as non-responders. In responders, we observed a statistically significant reduction not only of the values of DAS28 and CRP (p = 0.012 for both), ut also of plasma levels of FXIII (p = 0.05) and F1+2 (p = 0.025). In non-responders, all the studied parameters were unchanged. Conclusion The decrease of FXIII and F1+2 levels after tocilizumab treatment observed only in those patients who responded to the drug indicates that the effect of tocilizumab on the prothrombotic state is linked to the control of inflammation and disease activity and not to a direct effect of the drug, thus contributing to the reduction of the cardiovascular risk.
      PubDate: 2019-12-01
  • Comparison of Excimer Laser Versus Femtosecond Laser Assisted Trephination
           in Penetrating Keratoplasty: A Retrospective Study
    • Abstract: Introduction To compare the impact of non-mechanical excimer-assisted (EXCIMER) and femtosecond laser-assisted (FEMTO) trephination on outcomes after penetrating keratoplasty (PK). Methods In this retrospective study, 68 eyes from 23 females and 45 males (mean age at time of surgery, 53.3 ± 19.8 years) were included. Inclusion criteria were one surgeon (BS), primary central PK, Fuchs’ dystrophy (FUCHS) or keratoconus (KC), no previous intraocular surgery, graft oversize 0.1 mm and 16-bite double running suture. Trephination was performed using a manually guided 193-nm Zeiss Meditec MEL70 excimer laser (EXCIMER group: 18 FUCHS, 17 KC) or 60-kHz IntraLase™ femtosecond laser (FEMTO group: 16 FUCHS, 17 KC). Subjective refractometry (trial glasses) and corneal topography analysis (Pentacam HR; Casia SS-1000 AS-OCT; TMS-5) were performed preoperatively, before removal of the first suture (11.4 ± 1.9 months) and after removal of the second suture (22.6 ± 3.8 months). Results Before suture removal, mean refractive/AS-OCT topographic astigmatism did not differ significantly between EXCIMER and FEMTO. After suture removal, mean refractive/Pentacam/AS-OCT topographic astigmatism was significantly higher in the FEMTO (6.2 ± 2.9 D/7.1 ± 3.2 D/7.4 ± 3.3 D) than in the EXCIMER patients (4.3 ± 3.0 D/4.4 ± 3.1 D/4.0 ± 2.9 D) (p ≤ 0.005). Mean corrected distance visual acuity increased from 0.22 and 0.23 preoperatively to 0.55 and 0.53 before or 0.7 and 0.6 after suture removal in the EXCIMER and FEMTO groups, respectively. Differences between EXCIMER and FEMTO were only pronounced in the KC subgroup. Conclusion Non-mechanical EXCIMER trephination seems to have advantages regarding postoperative corneal astigmatism and visual acuity compared with FEMTO trephination, especially in KC. A bigger sample size and longer follow-up are needed to evaluate the long-term impact of EXCIMER and FEMTO trephination on postoperative topographic and visual outcomes.
      PubDate: 2019-12-01
  • Evaluation of the Cost Per Patient Achieving Treatment Targets with Oral
           Semaglutide: A Short-Term Cost-Effectiveness Analysis in the United States
    • Abstract: Introduction Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US. Methods Four endpoints were evaluated: (1) HbA1c ≤ 6.5%; (2) HbA1c < 7.0%; (3) ≥ 1.0%-point HbA1c reduction and weight loss ≥ 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target. Results Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide 14 mg was associated with lower cost of control than empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg by USD 15,036, 14,697, and 6996, respectively, and USD 931, 346 and 4497, respectively. For the double composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 525, 32,277 and 13,011, respectively versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg. For the triple composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 1255, 7510 and 5774, respectively. Conclusion Oral semaglutide was associated with lower cost of bringing patients with type 2 diabetes to four clinically-relevant treatment targets versus empagliflozin, sitagliptin, and liraglutide in the US. Funding Novo Nordisk A/S.
      PubDate: 2019-12-01
  • Efficacy and Safety of 8 Weeks of Glecaprevir/Pibrentasvir in
           Treatment-Naïve, HCV-Infected Patients with APRI ≤ 1 in a
           Single-Arm, Open-Label, Multicenter Study
    • Abstract: Introduction The presence or absence of cirrhosis in patients with chronic hepatitis C virus (HCV) infection influences the type and duration of antiviral therapy. Non-invasive markers, like serum aspartate aminotransferase (AST) to platelet ratio index (APRI), may help identify appropriate HCV treatment-naive patients for 8-week treatment with the pangenotypic regimen of glecaprevir/pibrentasvir. Methods This single-arm, open-label, international, prospective study (NCT03212521) evaluated the efficacy and safety of 8-week glecaprevir/pibrentasvir regimen in HCV treatment-naïve adults with chronic HCV genotypes 1–6 infection, APRI ≤ 1, and no prior evidence of cirrhosis. The primary and secondary outcomes were sustained virologic response at 12 weeks post-treatment (SVR12) by modified intent-to-treat (mITT) and intent-to-treat (ITT) analyses, respectively. Additional endpoints included virologic failures, treatment adherence, and genotype-specific SVR12 rates. Results Among the 230 patients enrolled, most were less than 65 years old (90%); 37% and 43% had a history of injection drug use or psychiatric disorders, respectively. SVR12 rates were 100% (222/222; 95% CI 98.3–100%) and 96.5% (222/230; 95% CI 94.2–98.9%) by mITT and ITT analyses, respectively. There were no virologic failures. ITT SVR12 rates were greater than 94% for all HCV genotypes. In patients with available data, treatment adherence was 99% (202/204). There were no grade 3 or higher laboratory abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin, and low rates of serious adverse events (2%). Conclusions Glecaprevir/pibrentasvir was highly efficacious and well tolerated in HCV treatment-naïve patients with APRI ≤ 1 and no prior evidence of cirrhosis. Trial Registration number, NCT03212521. Funding AbbVie. Plain Language Summary Plain language summary available for this article.
      PubDate: 2019-12-01
  • Real-World Effectiveness and Tolerability of Pazopanib as First Targeted
           Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Chart Review
           in Latin America
    • Abstract: Introduction Pazopanib is approved in Latin America as first targeted therapy for patients with metastatic renal cell carcinoma (mRCC). Methods A retrospective chart review of adult patients with mRCC who initiated pazopanib as first targeted therapy between January 2011 and March 2016 was conducted among oncology care centers in Argentina, Brazil, Chile, Colombia, and Mexico. Patient characteristics, treatment patterns, overall survival (OS), progression-free survival (PFS), and adverse events were summarized. Results A total of 156 charts of patients with mRCC receiving first-line pazopanib were reviewed (29, 54, 27, 28, and 18 patients from Argentina, Brazil, Chile, Colombia, and Mexico, respectively). The mean age at initial mRCC diagnosis was 61.6 years, 73.7% were male, and 51.3% were Hispanic. The median dose of pazopanib was 800 mg and the median time from initial mRCC diagnosis to pazopanib start was 2.2 months. The median time on treatment was 10.0 months. At the time of data extraction, 16.7% of patients remained on pazopanib, with clinical progression listed as the main reason for discontinuation. Subsequent therapy was received by 25.6% of patients; the most common were everolimus (9.6%) and axitinib (5.8%). Overall, median PFS and OS were 10.8 and 16.9 months, respectively, and varied across countries. The most common all-grade adverse events were diarrhea (44.9%), asthenia/fatigue (43.6%), and nausea (28.8%). Conclusions Pazopanib was used for first-line mRCC treatment in a clinically diverse patient population across Latin America. Real-world PFS and tolerability were similar to clinical studies of pazopanib. Funding Novartis Pharmaceuticals Corporation, Inc.
      PubDate: 2019-12-01
  • Effect of Orally Administered N -Acetylcysteine on Chronic Bronchitis: A
    • Abstract: Introduction The effect of N-acetylcysteine (NAC) treatment for patients with chronic bronchitis (CB) is controversial. To better understand the role of NAC in CB treatment, we performed a meta-analysis to provide a more accurate estimation of the importance of NAC treatment. Methods PubMed, Embase, and CNKI were systematically searched. The pooled relative risk (RR) and 95% confidence intervals (CI) were calculated using either fixed-effect model or random-effect model based on heterogeneity examination. Statistical analyses were performed using the STATA 12.0 and RevMan 5.2. Results A total of 11 publications with 775 patients who were taking NAC and 789 controls who were taking placebo were judged eligible regarding inclusion criteria. The pooled analysis demonstrated significant evidence that NAC reduced the frequency of CB exacerbations (RR = 0.81, 95% CI 0.69–0.93, P = 0.004). Patients treated with NAC had significant symptom improvement compared with controls (RR = 1.68, 95% CI 1.13–2.52, P = 0.01). NAC did not significantly increase the risk of adverse effects compared with placebo (RR 0.86, 95% CI 0.67–1.09, P = 0.22). Subgroup analysis was carried out to assess the stability of results. No publication bias was detected during analyses. Conclusion There is a role for NAC treatment in the management of CB by reducing symptoms and exacerbations compared with placebo, without increasing the risk of adverse effects. A regular treatment of low dosage (< 1200 mg per day) and a duration of at least 3 months seems to be effective.
      PubDate: 2019-12-01
  • Gender Disparities in Health Resource Utilization in Patients with
           Atherosclerotic Cardiovascular Disease: A Retrospective Cross-Sectional
    • Abstract: Introduction Gender disparities in access to healthcare have been documented, including disparities in access to care for cardiovascular diseases (CVDs). Disparities in access to cardiologists could disadvantage some patients to the newer lipid-lowering proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) antibodies, as utilization management criteria for PCSK9is often require step therapy with statins and/or ezetimibe and prescription by a cardiologist. To assess whether these utilization management criteria disproportionally limit access to patients with certain characteristics, we assessed the use of cardiologist care and receipt of statin and/or ezetimibe prescriptions from a cardiologist by gender and other patient demographic and clinical characteristics. Methods This cross-sectional study used administrative claims data from Inovalon’s Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry®) for patients enrolled in commercial and Medicare Advantage healthcare plans from January 1, 2014, through December 31, 2014. Provider data from the registry were linked to individual demographic and administrative claims data. Logistic regression models were used to assess characteristics associated with outpatient visits to a cardiologist and receipt of a prescription for statin and/or ezetimibe from a cardiologist. Results Data from 39,322 patients in commercial plans and 261,898 patients with Medicare Advantage were analyzed. Female gender (vs male) was associated with a significantly lower likelihood of visiting a cardiologist for patients in commercial plans (odds ratio [OR] 0.85; 95% confidence limit [CL] 0.81–0.88) and in Medicare Advantage plans (OR 0.82; 95% CL 0.81–0.83). Female gender was also associated with a lower likelihood of receiving a statin and/or ezetimibe prescription from a cardiologist for patients in commercial plans (OR 0.69; 95% CL 0.65–0.74) and in Medicare Advantage plans (OR 0.78; 95% CL 0.76–0.79). Conclusions Compared with men, women were less likely to visit a cardiologist and less likely to receive a prescription for a statin and/or ezetimibe from a cardiologist. Funding Amgen Inc.
      PubDate: 2019-12-01
  • A Budget Impact Model to Estimate the Environmental Impact of Adopting
           RESPIMAT ® Re-usable in the Nordics and Benelux
    • Abstract: Introduction The healthcare sector contributes 5–8% of the global greenhouse gas emissions. Global and regional organizations and governments have started to design and implement measures to reduce global greenhouse gas emissions in the healthcare sector, e.g. by green public procurement policies and inclusion of ecological considerations in the decision-making process for purchasing and funding of healthcare technologies. The objective of this study was to perform budget impact analysis of adopting RESPIMAT re-usable in the Nordics and Benelux that considered both the traditional healthcare costs as well as the environmental impact. Methods Inhaler costs and environmental impact over 5 years in the Nordics and Benelux in a scenario with RESPIMAT re-usable compared to a scenario without RESPIMAT re-usable were estimated using an budget impact model. RESPIMAT re-usable enables patients to re-use the inhaler device and its availability therefore reduces the number of inhalers and associated wastage. The carbon emissions were derived for each treatment pattern considering the whole life cycle (cradle-to-grave) of the inhaler product. The cost of carbon emissions was estimated using a societal cost per ton of carbon emission. Results Progressively introducing RESPIMAT re-usable in the Nordics and Benelux was estimated to decrease the number of inhalers used by 2023 by 7,466,621 compared to a scenario without RESPIMAT re-usable, which would result in a reduction of the environmental burden of inhaler use of 4717 tCO2e and a decrease in societal cost of €205,888. Conclusions Adopting RESPIMAT re-usable would lead to a substantial reduction in CO2 emissions, leading to savings from a societal perspective. Funding Boehringer Ingelheim.
      PubDate: 2019-12-01
  • Optimizing the Development Strategy of Combination Therapy in Respiratory
           Medicine: From Isolated Airways to Patients
    • Abstract: Abstract The current recommendations for the treatment of chronic obstructive pulmonary disease (COPD) are pushing towards triple combination therapy based on the combination of an inhaled corticosteroid (ICS) associated with two bronchodilator agents. However, dual bronchodilation remains the cornerstone for the treatment of most COPD patients. Combining a long-acting β2 adrenoceptor agonist (LABA) with a long-acting muscarinic antagonist (LAMA) induces appreciable synergistic bronchorelaxant effect in human airways, especially when the medications are combined at isoeffective concentrations. Thus, each LABA/LAMA combination is characterized by a specific range of concentration-ratio at which the drug mixture may induce sustained synergistic interaction. Results of a recent randomized controlled trial (RCT, NCT00696020) and evidences from pre-clinical studies in human isolated airways poses the question whether combining tiotropium 5 μg with olodaterol 5 μg is the best combination option: tiotropium/olodaterol 5/5 μg has the same efficacy profile of tiotropium/olodaterol 5/2 μg, and it is less effective than tiotropium/olodaterol 5/10 μg. Furthermore, tiotropium/olodaterol 5/2 μg, 5/5 μg, and 5/10 μg combinations are generally characterized by the same safety profile. Indeed tiotropium/olodaterol 5/5 μg is effective and safe in COPD, but a different development strategy based on solid data obtained from human isolated airways would have driven towards a better-balanced FDC to be tested in Phase III RCTs. Accurate bench-to-bedside plans are needed also in the development of triple combination therapies for asthma and COPD, in which the presence of an ICS in the formulation may further modulate the beneficial interaction between the LABA and the LAMA.
      PubDate: 2019-12-01
  • Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with
           Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine
    • Abstract: Estimates suggest that there are currently 122.8 million adults 65–99 years of age living with diabetes, of whom 90–95% are diagnosed with type 2 diabetes (T2D). Over the past two decades, a greater understanding of the complex and multifactorial pathogenesis of T2D has resulted in the development and introduction of new-generation classes of glucose-lowering therapies, which are now extensively endorsed by prevailing guidelines and are increasingly being used worldwide. These newer agents may further assist in the effective pharmacological management of T2D through the provision of patient-centered care that acknowledges multimorbidity and is respectful of and responsive to individual patient preferences and barriers. Given these considerations, the therapeutic approach in older patients with T2D is complex, particularly in those who have functional dependence, frailty, dementia, or who are at end-of-life. It is currently too early to draw conclusions on the long-term use of newer glucose-lowering agents in this population, as their efficacy and safety in older adults remains largely unknown. In this review, we will discuss considerations for the use of glucose-lowering treatments in older adults, with particular focus on the use of basal insulin and glucagon-like peptide-1 receptor agonists, and the rationale for the use of combination therapy comprising these agents. Finally, we will review clinical data from studies of the fixed-ratio combination of insulin glargine and lixisenatide in older patients with T2D. Funding Sanofi US, Inc.
      PubDate: 2019-12-01
  • Enhanced Safety Surveillance of GSK’s Quadrivalent Seasonal Influenza
           Vaccine in Belgium, Germany, and Spain for the 2018/19 Season: Interim
    • Abstract: Introduction Influenza is an important cause of morbidity and mortality in Europe. Prevention by annual vaccination is most effective but with yearly vaccine reformulation to match circulating virus strains, vaccine safety must be continuously monitored. The European Medicines Agency published guidance on safety monitoring of influenza vaccines. Methods An enhanced safety surveillance study of GSK’s inactivated quadrivalent influenza vaccine (IIV4) was conducted in Belgium, Germany, and Spain in influenza season 2018/19. The objective was to collect adverse event (AE) reports from subjects within 7 days of vaccination. A customized AE reporting card (AERC) with predefined AEs of interest was used to rapidly detect and evaluate potential new safety concerns. Interim results are presented here. Results Between week 40 and 52, 1060 vaccinated subjects were enrolled (31.0% Belgium, 26.2% Germany, and 42.7% Spain) covering all ages for which IIV4 is indicated (32.0% aged 6 months–17 years, 33.8% 18–65 years, and 34.2% over 65 years). Pediatric subjects  less than 9 years old (n = 139) received two doses. Following dose 1 and dose 2, 98.2% and 100%, respectively, returned the completed AERC recording any AEs. Following dose 1 and dose 2, 454 and 34 subjects, respectively, reported at least one AE (most frequently expected general and injection site symptoms and respiratory symptoms). Conclusion All reported AEs were expected as per summary product characteristics (smPC). No safety signals that impact public health or alter the benefit–risk profile of GSK’s IIV4 were identified. Subjects from all vaccinated age groups were enrolled and the use of AERCs allowed rapid monitoring and analysis of reported AEs. Trial Registration identifier, NCT03688620. Funding GlaxoSmithKline Biologicals SA.
      PubDate: 2019-12-01
  • Co-Creation of a Lanreotide Autogel/Depot Syringe for the Treatment of
           Acromegaly and Neuroendocrine Tumours Through Collaborative Human Factor
    • Abstract: Introduction Although the previous lanreotide autogel/depot syringe had been well received, feedback indicated that improvements could be made to make it more user-friendly. Additionally, the view that patients should have greater involvement in the research and development process is echoed by the International Neuroendocrine Cancer Alliance. A series of studies aimed to develop and validate a new syringe that works better for patients, caregivers and healthcare professionals (HCPs) by involving these groups at key stages in the development and testing process. Methods The multicentre, international, human factor studies, consisted of four formative studies and one validation study. The formative studies collected patient, caregiver and HCP feedback on the lanreotide autogel/depot syringe on the market at the time, and on newly designed prototypes. The validation study was conducted to evaluate the final syringe to confirm that it can be used effectively and safely in the intended environment, by the intended user, for the intended purpose. Results Overall, 213 individuals participated in the studies; 145 contributed to the formative studies and 68 to the validation study. The validated new-generation syringe included several important updates compared with the lanreotide autogel/depot syringe currently on the market, including the flanges, which are now larger and have a better grip; the overcap, which is white, ridged, opaque and bigger; the plunger supports and the thermoformed tray. No participant hurt themselves or others during the validation study (although several misuses were reported), and all participants succeeded in delivering a complete dose and activating the safety system. Conclusion With collaboration, a new syringe was developed to meet the needs of patients, caregivers and HCPs, whilst ensuring lanreotide was delivered effectively and safely. These studies highlight the importance of involving patients, caregivers and HCPs in clinical evaluation studies to develop medical products that address their concerns and meet their needs. Funding Ipsen. Plain Language Summary Plain language summary available for this article.
      PubDate: 2019-12-01
School of Mathematical and Computer Sciences
Heriot-Watt University
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