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    A case–control study is an observational study in which subjects are sampled based upon presence or absence of disease and then their prior exposure status is determined.
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    Case–control studies are statistically efficient and cost-effective for the study of rare diseases, and multiple risk factors can be investigated in a case–control study.
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    Newly diagnosed persons with disease are referred to as incident cases, whereas previously existing cases are referred to as prevalent cases.
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    Ideally, the controls should have a prevalence of exposure that is the same as the population of unaffected persons.
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    A population-based study is one in which cases and controls are sampled from a defined population, such as a metropolitan area.
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    A hospital-based sample of cases and controls may be convenient and inexpensive to collect, but may be biased by factors that affect the likelihood of hospitalization for cases and controls.
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    If sampling of cases, controls, or both is influenced by prior exposure history, then a selection bias may be present.
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    Confounding occurs when the apparent effect of the exposure of interest is attributable in whole or in part to some other factor.
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    Matching in a case–control study involves sampling of controls to parallel selected characteristics of cases in order to reduce the likelihood of confounding by the matched features.
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    The odds ratio is a measure of association between the exposure and disease that can be calculated in case–control studies.

image A 55-year-old woman was in excellent health until 2 weeks before admission, when she developed malaise, low-grade fever, cough, and generalized muscle pain. Although she took aspirin, her symptoms became worse over the next several days, in particular increased muscle pain, which made it very difficult for her to rise from a chair. She then consulted her personal physician, who performed a thorough evaluation. The patient’s history was unremarkable except for insomnia over the previous year, which she treated with self-prescribed l-tryptophan. On physical examination, she had mild, diffuse muscle tenderness and a mild, erythematous maculopapular rash over much of her body. Laboratory examination was remarkable for elevations of her blood eosinophil count (2000 cells per mm3, < 250 cells per mm3) and mildly elevated aldolase levels. Eosinophilia-myalgia syndrome (EMS) was diagnosed.

In November 1989, researchers from the Centers for Disease Control and Prevention (CDC) and local health departments published the first description of EMS. This newly recognized syndrome is characterized by incapacitating myalgias (muscle pains), elevated eosinophil counts, and in some patients, arthralgias (joint pains), skin thickening, hair loss, and interstitial lung disease.

EMS was first recognized in October 1989, when astute physicians determined that three people with unexplained myalgias and eosinophilia had consumed l-tryptophan, an essential amino acid available without prescription in drug and health food stores. Prompt response by health departments quickly led to case–control studies, the results of which suggested that ingestion of l-tryptophan was the cause of EMS. l-Tryptophan–containing products ...

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