There are numerous definitions of polypharmacy to describe the use of many medications among older adults, but there is a need to clarify if they are purposive and meaningful. By means of a systematic review, we identified definitions of polypharmacy used in multimorbid older adults (≥65 years). We evaluated if the definitions align among the domains of research, clinical practice, and public health and appraised whether concepts of polypharmacy are based on strong foundations. More than 46 definitions of polypharmacy were retrieved from 348 publications (research: n = 243; clinical practice: n = 88; public health: n = 17). Several thresholds based on the number of medications were mentioned. The majority of the publications (n = 202, 58%) used a minimal threshold of five medications. Heterogeneous qualitative definitions were identified, mostly stating that polypharmacy is “more drugs than needed”. There was no significant divergence between domains as to the type of definitions used, although qualitative definitions were more common in clinical practice. Nearly half (n = 156, 47%) of the publications provided no justification for the polypharmacy definition used. The wide variety of definitions for polypharmacy precludes comparisons, appropriate identification and management of polypharmacy in multimorbid older adults. Standardized definitions would allow more coherent judgments regarding the individual and collective stakes of polypharmacy.
Immunotherapy of tumors and of melanoma in particular has a long history, and recently this therapeutic approach found a reliable scientific rationale. This biological therapy aims to teach the patient's immune system to recognize the antigens expressed on tumor cells and destroy them, leaving normal cells intact. The success of this therapy highly depends on the selection of target antigens that are essential for tumors growth and progression. The overexpression of GM(3) ganglioside 1 and especially the expression of its metabolite GM(3) lactone 2 characterize murine and human melanomas, playing an important role in tumor progression and making such self-antigens potential targets for the immunotherapy of these neoplasms. Although more immunogenic than its precursor, GM(3) lactone 2 is unsuitable to be used in immunotherapy as a melanoma-associated antigen (MAA) because it is unstable under physiological conditions. We designed and synthesized the hydrolytically stable mimetic 3, which is remarkably simpler than the native lactone 2; after conjugation of 3 to the protein carrier keyhole-limpet hemocyanin (KLH), the obtained glycoprotein 5 was used as the immunogen in vivo to successfully elicit specific antimelanoma antibodies. In fact, no appreciable binding to GM(1) was observed. Capitalizing on the stability and on the reduced structural complexity of mimetic 3, the immunostimulant 5 we report represents a new promising synthetic glycoconjugate for the immunotherapy of melanoma.
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