Users' guides to the medical literature: XXIV. How to use an article on the clinical manifestations of disease

Clinicians rely on knowledge about the clinical manifestations of disease to make clinical diagnoses. Before using research on the frequency of clinical features found in patients with a disease, clinicians should appraise the evidence for its validity, results, and applicability. For validity, 4 issues are important - how the diagnoses were verified, how the study sample relates to all patients with the disease, how the clinical findings were sought, and how the clinical findings were characterized. Ideally, investigators will verify the presence of disease in study patients using credible criteria that are independent of the clinical manifestations under study. Also, ideally the study patients will represent the full spectrum of the disease, undergo a thorough and consistent search for clinical findings, and these findings will be well characterized in nature and timing. The main results of these studies are expressed as the number and percentages of patients with each manifestation. Confidence intervals can describe the precision of these frequencies. Most clinical findings occur with only intermediate frequency, and since these frequencies are equivalent to diagnostic sensitivities, this means that the absence of a single finding is rarely powerful enough to exclude the disease. Before acting on the evidence, clinicians should consider whether it applies to their own patients and whether it has been superseded by new developments. Detailed knowledge of the clinical manifestations of disease should increase clinicians' ability to raise diagnostic hypotheses, select differential diagnoses, and verify final diagnoses.