Towards a Dynamic Definition of Health and Disease

A multifactorial and growing crisis of health care systems in the developed world has affected medicine. In order to provide rational responses, some central concepts of the past, such as the definitions of health and disease, need to be updated. For this purpose physicians should initiate a new debate. As a point of departure the following definitions are proposed: Health is a dynamic state of wellbeing characterized by a physical, mental and social potential, which satisfies the demands of a life commensurate with age, culture, and personal responsibility. If the potential is insufficient to satisfy these demands the state is disease. This term includes sickness, illness, ill health, and malady. The described potential is divided into a biologically given and a personally acquired partial potential. Their proportions vary throughout the life cycle. The proposed definitions render it empirically possible to diagnose persons as healthy or diseased and to apportion some of the responsibility for their state of health to individuals themselves. Treatment strategies should always consider three therapeutic routes: improvements of the biologically given and of the personally acquired partial potentials and adaptations of the demands of life. These consequences favourably contrast with those resulting from the WHO-definition of healt

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

Überempfindlichkeitsreaktionen auf Arzneimittel müssen ausreichend geklärt werden mit dem Ziel, den Auslöser zu identifizieren. Die Anamnese umfasst neben der allgemeinen Anamnese auch Informationen zu angewandten Arzneimitteln, zur Klassifikation und zu den Umständen der Reaktion. Hauttests erfolgen bei allen Reaktionen mit Symptomen allergischer Überempfindlichkeiten mit geeigneten Testkonzentrationen, möglichst zwischen 4 Wochen und 6 Monate nach Abheilung der Reaktion durch Pricktest, Intrakutantest, Epikutantest oder Photopatchtest. Validierte Tests zum Nachweis spezifischer IgE-Antikörper im Serum sind nur für wenige Arzneistoffe (vor allem Betalaktamantibiotika) verfügbar; andere immunologische Labormethoden, z.B. der Basophilen-Aktivierungstest, werden nur in ausgewählten Fällen angewendet. Provokationstests sind indiziert, wenn der Auslöser durch bisherige Untersuchungen nicht mit Sicherheit identifiziert werden kann. Die Bewertung der Ergebnisse von Provokationstests sollte möglichst anhand objektiver Parameter erfolgen. Das Ergebnis der abschließenden Gesamtbeurteilung wird mit dem Patienten ausführlich besprochen und in einem Allergiepass niedergeleg

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

Drug hypersensitivity reactions have to be tested to identify the culprit substance. The history includes the general information and specific data concerning used drugs, the classification and circumstances of the reaction. Skin tests are performed in all hypersensitivity reactions with allergic symptoms. Tests should be done between four weeks and six months after clearance of the symptoms by performing skin prick test, intradermal test, patch test or photopatch test. Validated tests for the detection of specific IgE antibodies in the serum are available for only few drugs, especially betalactam antibiotics. Other laboratory tests, e.g., the basophil activation test are done only in special cases. Provocation tests are indicated, if the culprit drug cannot be identified by the above mentioned tests. If possible, the evaluation of provocation tests should rely on objective parameters. The concluding assessment will be discussed with the patient and will be documented in an allergy pass

Clinical Characterization and Diagnostic Approaches for Patients Reporting Hypersensitivity Reactions to Quinolones

[EN] BACKGROUND: Quinolones are the second most frequent cause of hypersensitivity reactions (HSRs) to antibiotics. A marked increase in the number of patients with HSRs to quinolones has been detected. OBJECTIVE: To describe the clinical characteristics of patients with HSRs to quinolones and present methods for their diagnosis. METHODS: Patients attending the allergy unit due to reactions suggestive of HSRs to quinolones were prospectively evaluated between 2005 and 2018. Diagnosis was achieved using clinical history, skin tests (STs), basophil activation tests (BATs), and drug provocation tests (DPTs) if ST and BAT results were negative. RESULTS: We included 128 subjects confirmed as having HSRs to quinolones and 42 found to be tolerant. Anaphylaxis was the most frequent entity in immediate HSRs and was most commonly induced by moxifloxacin. Patients were evaluated a median of 150 days (interquartile range, 60-365 days) after the reaction. Of patients who underwent ST and BAT, 40.7% and 70%, respectively, were positive. DPT with a quinolone was performed in 48 cases, giving results depending on the culprit drug: when moxifloxacin was involved, 62.5% of patients gave a positive DPT result to ciprofloxacin, whereas none reacted to levofloxacin. The risk of HSR was 96 times higher in subjects who reported moxifloxacin-induced anaphylaxis and 18 times higher in those reporting immediate reactions compared with clinical entities induced by quinolones other than moxi-floxacin and nonimmediate reactions. CONCLUSIONS: The diagnosis of HSR to quinolones is complex. The use of clinical history is essential as a first step. BAT shows higher sensitivity than STs. DPTs can be useful for finding safe alternative quinolones.The present study has been supported by the Institute of Health "Carlos III" of the Ministry of Economy and Competitiveness (grants cofounded by European Regional Development Fund: RETIC ARADYALRD16/0006/0001, RD16/0006/0010, RD16/0006/0019, and RD16/0006/0030). I.D. is a clinical investigator (B0001-2017) from Consejeria de Salud of the Andalusian government, Junta de Andalucia. N.P.-S. holds a Rio Hortega research contract (CM17/0014), and E.B. a Juan Rodes research contract (JR18/00049), both from the Institute of Health "Carlos III," Spanish Ministry of Economy and Competitiveness (grants cofounded by the European Social Fund).Doña, I.; Pérez-Sánchez, N.; Salas, M.; Barrionuevo, E.; Ruiz-San Francisco, A.; Hernández Fernández De Rojas, D.; Martí-Garrido, J.... (2020). Clinical Characterization and Diagnostic Approaches for Patients Reporting Hypersensitivity Reactions to Quinolones. Journal of Allergy and Clinical Immunology: In Practice. 8(8):2707-2714. https://doi.org/10.1016/j.jaip.2020.04.051S2707271488Campi, P., & Pichler, W. J. (2003). Quinolone hypersensitivity. Current Opinion in Allergy and Clinical Immunology, 3(4), 275-281. doi:10.1097/00130832-200308000-00007Zhanel, G. G., Ennis, K., Vercaigne, L., Walkty, A., Gin, A. S., Embil, J., … Hoban, D. J. (2002). A Critical Review of the Fluoroquinolones. Drugs, 62(1), 13-59. doi:10.2165/00003495-200262010-00002Bertino, J., & Fish, D. (2000). The safety profile of the fluoroquinolones. Clinical Therapeutics, 22(7), 798-817. doi:10.1016/s0149-2918(00)80053-3Ho, D. Y., Song, J. C., & Wang, C. C. (2003). Anaphylactoid Reaction to Ciprofloxacin. Annals of Pharmacotherapy, 37(7-8), 1018-1023. doi:10.1345/aph.1c498Demoly, P., Adkinson, N. F., Brockow, K., Castells, M., Chiriac, A. M., Greenberger, P. A., … Thong, B. Y.-H. (2014). International Consensus on drug allergy. Allergy, 69(4), 420-437. doi:10.1111/all.12350Schmid, D. A., Depta, J. P. H., & Pichler, W. J. (2006). T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity. Clinical Experimental Allergy, 36(1), 59-69. doi:10.1111/j.1365-2222.2006.02402.xJones, S. C., Budnitz, D. S., Sorbello, A., & Mehta, H. (2013). US-based emergency department visits for fluoroquinolone-associated hypersensitivity reactions. Pharmacoepidemiology and Drug Safety, 22(10), 1099-1106. doi:10.1002/pds.3499Sachs, B., Fischer-Barth, W., & Merk, H. F. (2015). Reporting rates for severe hypersensitivity reactions associated with prescription-only drugs in outpatient treatment in Germany. Pharmacoepidemiology and Drug Safety, 24(10), 1076-1084. doi:10.1002/pds.3857McNeil, B. D., Pundir, P., Meeker, S., Han, L., Undem, B. J., Kulka, M., & Dong, X. (2014). Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature, 519(7542), 237-241. doi:10.1038/nature14022Van Gasse, A. L., Sabato, V., Uyttebroek, A. P., Elst, J., Faber, M. A., Hagendorens, M. M., … Ebo, D. G. (2017). Immediate moxifloxacin hypersensitivity: Is there more than currently meets the eye? Allergy, 72(12), 2039-2043. doi:10.1111/all.13236Porebski, G., Kwiecien, K., Pawica, M., & Kwitniewski, M. (2018). Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2) in Drug Hypersensitivity Reactions. Frontiers in Immunology, 9. doi:10.3389/fimmu.2018.03027González-Gregori, R., Dolores Hernández Fernandez De Rojas, M., López-Salgueiro, R., Díaz-Palacios, M., & García, A. N. (2012). Allergy alerts in electronic health records for hospitalized patients. Annals of Allergy, Asthma & Immunology, 109(2), 137-140. doi:10.1016/j.anai.2012.06.006Renaudin, J.-M., Beaudouin, E., Ponvert, C., Demoly, P., & Moneret-Vautrin, D.-A. (2013). Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy, 68(7), 929-937. doi:10.1111/all.12168Blanca-López, N., Ariza, A., Doña, I., Mayorga, C., Montañez, M. I., Garcia-Campos, J., … Torres, M. J. (2013). Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved. Clinical & Experimental Allergy, 43(5), 560-567. doi:10.1111/cea.12099Johannes, C. B., Ziyadeh, N., Seeger, J. D., Tucker, E., Reiter, C., & Faich, G. (2007). Incidence of Allergic Reactions Associated with Antibacterial Use in a Large, Managed Care Organisation. Drug Safety, 30(8), 705-713. doi:10.2165/00002018-200730080-00007Kulthanan, K., Chularojanamontri, L., Manapajon, A., Dhana, N., & Jongjarearnprasert, K. (2011). Cutaneous Adverse Reactions to Fluoroquinolones. Dermatitis, 22(3), 155-160. doi:10.2310/6620.2011.10115Neuman, M. G., Cohen, L. B., & Nanau, R. M. (2015). Quinolones-induced hypersensitivity reactions. Clinical Biochemistry, 48(10-11), 716-739. doi:10.1016/j.clinbiochem.2015.04.006Phillips, C. J., Gilchrist, M., Cooke, F. J., Franklin, B. D., Enoch, D. A., Murphy, M. E., … Holmes, A. H. (2019). Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts. BMJ Open, 9(2), e026624. doi:10.1136/bmjopen-2018-026624Dávila, I., Diez, M. L., Quirce, S., Fraj, J., Hoz, B., & Lazaro, M. (1993). Cross-reactivity between quinolones. Allergy, 48(5), 388-390. doi:10.1111/j.1398-9995.1993.tb02413.xScherer, K., & Bircher, A. J. (2005). Hypersensitivity reactions to fluoroquinolones. Current Allergy and Asthma Reports, 5(1), 15-21. doi:10.1007/s11882-005-0049-1Brockow, K., Garvey, L. H., Aberer, W., Atanaskovic-Markovic, M., Barbaud, A., … Bilo, M. B. (2013). Skin test concentrations for systemically administered drugs - an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy, 68(6), 702-712. doi:10.1111/all.12142Manfredi, M., Severino, M., Testi, S., Macchia, D., Ermini, G., Pichler, W. J., & Campi, P. (2004). Detection of specific IgE to quinolones. Journal of Allergy and Clinical Immunology, 113(1), 155-160. doi:10.1016/j.jaci.2003.09.035Aranda, A., Mayorga, C., Ariza, A., Doña, I., Rosado, A., Blanca-Lopez, N., … Torres, M. J. (2010). In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy, 66(2), 247-254. doi:10.1111/j.1398-9995.2010.02460.xBen Said, B., Berard, F., Bienvenu, J., Nicolas, J.-F., & Rozieres, A. (2010). Usefulness of basophil activation tests for the diagnosis of IgE-mediated allergy to quinolones. Allergy, 65(4), 535-536. doi:10.1111/j.1398-9995.2009.02213.xMayorga, C., Celik, G., Rouzaire, P., Whitaker, P., Bonadonna, P., … Rodrigues-Cernadas, J. (2016). In vitrotests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy, 71(8), 1103-1134. doi:10.1111/all.12886Seitz, C. S., Bröcker, E. B., & Trautmann, A. (2009). Diagnostic testing in suspected fluoroquinolone hypersensitivity. Clinical & Experimental Allergy, 39(11), 1738-1745. doi:10.1111/j.1365-2222.2009.03338.xBrockow, K., Ardern‐Jones, M. R., Mockenhaupt, M., Aberer, W., Barbaud, A., Caubet, J., … Mortz, C. G. (2018). EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity. Allergy, 74(1), 14-27. doi:10.1111/all.13562Valdivieso, R., Pola, J., Losada, E., Subiza, J., Armentia, A., & Zapata, C. (1988). Severe anaphylactoid reaction to nalidixic acid. Allergy, 43(1), 71-73. doi:10.1111/j.1398-9995.1988.tb02046.xAberer, W., Bircher, A., Romano, A., Blanca, M., Campi, P., … Fernandez, J. (2003). Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy, 58(9), 854-863. doi:10.1034/j.1398-9995.2003.00279.xSALVO, F., POLIMENI, G., CUTRONEO, P., LEONE, R., CONFORTIC, A., MORETTI, U., … CAPUTI, A. (2008). Allergic reactions to oral drugs: A case/non-case study from an Italian spontaneous reporting database (GIF). Pharmacological Research, 58(3-4), 202-207. doi:10.1016/j.phrs.2008.07.003Blanca, M., Romano, A., Torres, M. J., Férnandez, J., Mayorga, C., Rodriguez, J., … Atanasković-Marković, M. (2009). Update on the evaluation of hypersensitivity reactions to betalactams. Allergy, 64(2), 183-193. doi:10.1111/j.1398-9995.2008.01924.xBircher, A. J., & Scherer Hofmeier, K. (2012). Drug hypersensitivity reactions: Inconsistency in the use of the classification of immediate and nonimmediate reactions. Journal of Allergy and Clinical Immunology, 129(1), 263-264. doi:10.1016/j.jaci.2011.08.042Terrados, S., Blanca, M., Garcia, J., Vega, J., Torres, M. J., Carmona, M. J., … Fernandez, J. (1995). Nonimmediate reactions to betalactams: prevalence and role of the different penicillins. Allergy, 50(7), 563-567. doi:10.1111/j.1398-9995.1995.tb01200.xGómez, E., Blanca-Lopez, N., Salas, M., Canto, G., Campo, P., Torres, M. J., … Blanca, M. (2013). Induction of accelerated reactions to amoxicillin by T-cell effector mechanisms. Annals of Allergy, Asthma & Immunology, 110(4), 267-273. doi:10.1016/j.anai.2013.01.003Blanca-López, N., Pérez-Sánchez, N., Agúndez, J. A., García-Martin, E., Torres, M. J., Cornejo-García, J. A., … Doña, I. (2016). Allergic Reactions to Metamizole: Immediate and Delayed Responses. International Archives of Allergy and Immunology, 169(4), 223-230. doi:10.1159/000444798Alonso, M. D., Martín, J. A., Quirce, S., Dávila, I., Lezaun, A., & Cano, M. S. (1993). Fixed eruption caused by ciprofloxacin with cross-sensitivity to norfloxacin. Allergy, 48(4), 296-297. doi:10.1111/j.1398-9995.1993.tb00733.xDavila, G., Ruiz-Hornillos, J., Rojas, P., De Castro, F., & Zubeldia, J. M. (2009). TOXIC EPIDERMAL NECROLYSIS INDUCED BY LEVOFLOXACIN. Annals of Allergy, Asthma & Immunology, 102(5), 441-442. doi:10.1016/s1081-1206(10)60521-2Ayllón, M. L., Martinez, M. G., Mosquera, M. R., Laguna Martinez, J. J., Martiartu, M. O., & Fernández de Miguel, C. (1995). Fixed eruption caused by ciprofloxacin without cross-sensitivity to norfloxacin. Allergy, 50(7), 598-599. doi:10.1111/j.1398-9995.1995.tb01206.xEmpedrad, R. (2003). Nonirritating intradermal skin test concentrations for commonly prescribed antibiotics. Journal of Allergy and Clinical Immunology, 112(3), 629-630. doi:10.1016/s0091-6749(03)01783-4Brož, P., Harr, T., Hecking, C., Grize, L., Scherer, K., Jaeger, K. A., & Bircher, A. J. (2012). Nonirritant intradermal skin test concentrations of ciprofloxacin, clarithromycin, and rifampicin. Allergy, 67(5), 647-652. doi:10.1111/j.1398-9995.2012.02807.xUyttebroek, A. P., Sabato, V., Bridts, C. H., De Clerck, L. S., & Ebo, D. G. (2015). Moxifloxacin hypersensitivity: Uselessness of skin testing. The Journal of Allergy and Clinical Immunology: In Practice, 3(3), 443-445. doi:10.1016/j.jaip.2014.12.012Fernandez-Rivas, M. (1997). Fixed drug eruption (FDE) caused by norfloxacin. Allergy, 52(4), 477-478. doi:10.1111/j.1398-9995.1997.tb01035.xChang, B., Knowles, S. R., & Weber, E. (2010). Immediate Hypersensitivity to Moxifloxacin with Tolerance to Ciprofloxacin: Report of Three Cases and Review of the Literature. Annals of Pharmacotherapy, 44(4), 740-745. doi:10.1345/aph.1m579Sánchez-Morillas, L., Rojas Pérez-Ezquerra, P., Reaño-Martos, M., Laguna-Martínez, J. J., & Gómez-Tembleque, P. (2010). Systemic anaphylaxis caused by moxifloxacin. Allergologia et Immunopathologia, 38(4), 226-227. doi:10.1016/j.aller.2009.09.00

Assessing agro-ecological practices using a combination of three sustainability assessment tools

This paper is based on results from the research project UNISECO, which is funded by European Union’s Horizon 2020 research and innovation programme under grant agreement No. 773901.We would like to thank all the farmers, farm organisations and stakeholders of the multi-actor platforms of the UNISECO project who contributed to the data collection. We also like to thank Andreas Basler whose corrections improved the comprehensibility of the paper.Peer reviewedPublisher PD

Health and Disease—Emergent States Resulting From Adaptive Social and Biological Network Interactions

Health is an adaptive state unique to each person. This subjective state must be distinguished from the objective state of disease. The experience of health and illness (or poor health) can occur both in the absence and presence of objective disease. Given that the subjective experience of health, as well as the finding of objective disease in the community, follow a Pareto distribution, the following questions arise: What are the processes that allow the emergence of four observable states—(1) subjective health in the absence of objective disease, (2) subjective health in the presence of objective disease, (3) illness in the absence of objective disease, and (4) illness in the presence of objective disease? If we consider each individual as a unique biological system, these four health states must emerge from physiological network structures and personal behaviors. The underlying physiological mechanisms primarily arise from the dynamics of external environmental and internal patho/physiological stimuli, which activate regulatory systems including the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Together with other systems, they enable feedback interactions between all of the person's system domains and impact on his system's entropy. These interactions affect individual behaviors, emotional, and cognitive responses, as well as molecular, cellular, and organ system level functions. This paper explores the hypothesis that health is an emergent state that arises from hierarchical network interactions between a person's external environment and internal physiology. As a result, the concept of health synthesizes available qualitative and quantitative evidence of interdependencies and constraints that indicate its top-down and bottom-up causative mechanisms. Thus, to provide effective care, we must use strategies that combine person-centeredness with the scientific approaches that address the molecular network physiology, which together underpin health and disease. Moreover, we propose that good health can also be promoted by strengthening resilience and self-efficacy at the personal and social level, and via cohesion at the population level. Understanding health as a state that is both individualized and that emerges from multi-scale interdependencies between microlevel physiological mechanisms of health and disease and macrolevel societal domains may provide the basis for a new public discourse for health service and health system redesign