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Primary care physicians are often taxed by patient complaints that do not seem to have a clear etiology, nor do the patients improve despite good medications and expensive procedures. Current studies show that stress or distress may have a significant effect on the onset, the course, and the management of many, if not all, diseases. Understanding patient's underlying stress physiology and coping mechanisms may enable physicians to better understand various clinical disorders and treat their manifested symptoms. Evidence is reviewed by which stress may exacerbate or cause illness and by which behavioral medicine interventions can improve clinical outcomes.