Sensitivity and specificity in the context of "Diagnostic method"

Medical diagnosis (abbreviated Dx, D_x, or D_s) is the process of determining which disease or condition explains a person's symptoms and signs. It is most often referred to as a diagnosis with the medical context being implicit. The information required for a diagnosis is typically collected from a history and physical examination of the person seeking medical care. Often, one or more diagnostic procedures, such as medical tests, are also done during the process. Sometimes the posthumous diagnosis is considered a kind of medical diagnosis.

Diagnosis is often challenging because many signs and symptoms are nonspecific. For example, redness of the skin (erythema), by itself, is a sign of many disorders and thus does not tell the healthcare professional what is wrong. Thus differential diagnosis, in which several possible explanations are compared and contrasted, must be performed. This involves the correlation of various pieces of information followed by the recognition and differentiation of patterns. Occasionally the process is made easy by a sign or symptom (or a group of several) that is pathognomonic.

Trousseau sign of latent tetany is a medical sign observed in patients with low calcium. From 1 to 4 percent of normal patients will test positive for Trousseau's sign of latent tetany. This sign may be positive before other manifestations of hypocalcemia such as hyperreflexia and tetany, as such it is generally believed to be more sensitive (94%) than the Chvostek sign (29%) for hypocalcemia. This sign may also be observed as a symptom of hyperventilation syndrome as a result of hypocapnia-induced reduction of calcium levels in the blood.

To elicit the sign, a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm. The wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct. The sign is also known as main d'accoucheur (French for "hand of the obstetrician") because it supposedly resembles the position of an obstetrician's hand in delivering a baby.

Chemoproteomics (also known as chemical proteomics) entails a broad array of techniques used to identify and interrogate protein-small molecule interactions. Chemoproteomics complements phenotypic drug discovery, a paradigm that aims to discover lead compounds on the basis of alleviating a disease phenotype, as opposed to target-based drug discovery (reverse pharmacology), in which lead compounds are designed to interact with predetermined disease-driving biological targets. As phenotypic drug discovery assays do not provide confirmation of a compound's mechanism of action, chemoproteomics provides valuable follow-up strategies to narrow down potential targets and eventually validate a molecule's mechanism of action. Chemoproteomics also attempts to address the inherent challenge of drug promiscuity in small molecule drug discovery by analyzing protein-small molecule interactions on a proteome-wide scale. A major goal of chemoproteomics is to characterize the interactome of drug candidates to gain insight into mechanisms of off-target toxicity and polypharmacology.

Chemoproteomics assays can be stratified into three basic types. Solution-based approaches involve the use of drug analogs that chemically modify target proteins in solution, tagging them for identification. Immobilization-based approaches seek to isolate potential targets or ligands by anchoring their binding partners to an immobile support. Derivatization-free approaches aim to infer drug-target interactions by observing changes in protein stability or drug chromatography upon binding. Computational techniques complement the chemoproteomic toolkit as parallel lines of evidence supporting potential drug-target pairs, and are used to generate structural models that inform lead optimization. Several targets of high profile drugs have been identified using chemoproteomics, and the continued improvement of mass spectrometer sensitivity and chemical probe technology indicates that chemoproteomics will play a large role in future drug discovery.