Epidemiology Informing Clinical Practice

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Epidemiology Informing Clinical Practice
The earliest observations on population patterns of disease and how they might inform medical practice probably occurred during the 17th century, and they continue to the present day, with increasing relevance to nutritional and infectious diseases, and cancer and other chronic diseases. Chronic-disease methods grew out of infectious-disease epidemiology, in which both field and laboratory methods are used. In diseases where intermediate biology was not initially observable (particularly cancer), record-based and interview-based epidemiology revealed some key exposures (e.g. smoking and radiation). With measurable intermediates (e.g. blood lipids), cardiovascular epidemiology also yielded inferences on causal pathways. Important changes that are remaking the field of epidemiology and will ultimately influence all aspects of medical practice include the following: high-throughput genotyping, allowing genetic and gene-environment causes of disease to be identified; high-throughput proteomics, which should allow the development of early-detection methods; new tools for the measurement of exposures; and a molecular basis for disease taxonomy. These new methods will allow a much better understanding of both the etiology and the intermediate stages of disease; however, new methods do not obviate the necessity for good study design, especially the need to be clear on the difference between observation and experiment. The greatest opportunities to inform medical practice come from the application of new methods to large-scale human observational studies, which include genetics, environment, early-detection markers, molecular classification of outcome, and treatment data. Improved molecular classification of disease will allow smaller, focused clinical trials to be undertaken and, ultimately, the tailoring of treatment to the biological profile of patient and disease.

The use of epidemiology to inform clinical practice probably began with John Graunt in 1662. Graunt was a London haberdasher who wrote a superb treatise: Natural and Political OBSERVATIONS Mentioned in a following Index, and made upon the Bills of Mortality By JOHN GRAUNT, Citizen of LONDON. With reference to the Government, Religion, Trade, Growth, Ayre, Diseases, and the several Changes of the said CITY. This was the first description of the patterns of causes of death. It provided a template for the systematic collection of data on patterns of disease and death, and allowed future demographic and epidemiological researchers to ask questions such as 'Why is this cause of death more important than that cause in this population?', 'Why are there differences in disease patterns between populations?', 'What are the primary causes of mortality among the young, the middle-aged and the elderly, and among men and women?' and, ultimately, 'What are the causes of this particular disease?'

At around the same time, astute clinical practitioners had also begun to think about disease causation in a systematic way, providing descriptions of occupational cancer and nutritional-deficiency diseases. In his De Morbis Artificum, Bernardino Rammazzini noted the excess risk of breast cancer in nuns. Percival Pott attributed scrotal cancer in chimney sweeps to their occupational exposure to soot and the fact that, in the absence of bathing and clean clothes, it accumulated in their clothing, and rejected a diagnosis of venereal disease as suggested by his colleagues. In the 18th century, James Lind showed that scurvy was a deficiency disease. The great navigator James Cook, aware of this work, pioneered the use of fresh food and lemon juice (oddly recorded in history as lime juice and giving British sailors the nickname 'limeys') to fend off scurvy; Cook never lost a man to this disease. The germ theory of disease in the 19th century provided a biological framework from which to hang more elaborate postulates about the relationships between causative exposures and the nature of disease processes. Thus were born the ancestors of the case-control study.

The turn of the 20th century marked the birth of systematic studies that identified causes of both infectious and deficiency diseases. Thiamine (vitamin B1) was the first vitamin to be discovered. Kanehiro Takaki, in Japan, first recognized beri beri as a nutritional disease related to excess consumption of polished rice, but attributed it to a diet poor in protein. The signs and symptoms of beri beri included muscle weakness, weight loss, nervous-system abnormalities and, ultimately, paralysis and death. Astute observation gave Christian Eijkman a clue; he noticed chickens with similar signs. Normally, the chickens were fed cheaper unprocessed (unpolished) rice, but those with signs of beri beri had been fed white rice and little else. He postulated that an ingredient in rice bran prevented the disease. Eventually, thiamine and other B vitamins were isolated in pure form. Awareness of a population-wide disorder, astute clinical observation, and a combination of animal observation and experimentation eventually allowed the prevention of this disease.

Yellow fever has been recognized for perhaps 400 years. Infection causes a wide spectrum of disease, from mild symptoms to severe illness and death; the 'yellow' is the result of the jaundice that affects some patients. Yellow fever is a viral hemorrhagic disease transmitted by infected mosquitoes. In 1900, the US Army Yellow Fever Commission (often called The Reed Commission after its leader, Walter Reed) established that the Aedes aegypti mosquito was the vector for the agent, and refuted the popular notions that yellow fever was spread by direct contact or by 'contaminated' objects. This finding resulted in systematic efforts toward the eradication of the Aedes mosquito.

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