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New or unexplained symptoms account for about half of all office visits. Evidence-based symptom evaluation combines knowledge of a symptom's clinical epidemiology with disease candidates according to Bayesian principles, such that the likelihood of a specific disease is a function of patient demographics, comorbidities, and clinical features. This knowledge supports decisions about further testing or treatment or whether to perform additional testing before treatment.

Biological, psychological, social, and cultural factors affect how patients experience, interpret, and describe symptoms, and whether their symptoms are sufficiently bothersome or worrisome to seek medical attention. Host and environmental factors can influence the symptoms that are manifested. For example, in 1967, Evans proposed five "realities" that reflect the conundrum clinicians face when associating an acute respiratory syndrome with an etiologic pathogen: (1) The same clinical syndrome may be produced by a variety of infectious pathogens; (2) the same pathogen may produce a variety of syndromes; (3) the most likely cause of a syndrome may vary by patient age, year, geography, and setting; (4) diagnosis of the pathogen is frequently impossible on the basis of clinical findings alone; and (5) the causes of a large proportion of infectious disease syndromes are still unknown.

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