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J Hand Surg Am. 2008 Apr;33(4):525-38. doi: 10.1016/j.jhsa.2008.01.004.

The quality and strength of evidence for etiology: example of carpal tunnel syndrome.

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  • 1Department of Orthopaedic Surgery, Hand and Upper Extremity Service, Massachusetts General Hospital, Boston, MA, USA.



The purpose of this investigation was to evaluate the quality and strength of scientific evidence supporting an etiologic relationship between a disease and a proposed risk factor using a scoring system based on the Bradford Hill criteria for causal association.


A quantitative score based on the Bradford Hill criteria (qBHs) was used to evaluate 117 articles presenting original data regarding the etiology of carpal tunnel syndrome: 33 (28%) that evaluated biological (structural or genetic) risk factors, 51 (44%) that evaluated occupational (environment or activity-related) risk factors, and 33 (28%) that evaluated both types of risk factors.


The quantitative Bradford Hill scores of 2 independent observers showed very good agreement, supporting the reliability of the instrument. The average qBHs was 12.2 points (moderate association) among biological risk factors compared with 5.2 points (poor association) for occupational risk factors. The highest average qBHs was observed for genetic factors (14.2), race (11.7), and anthropometric measures of the wrist (11.3 points) with all studies finding a moderate causal association. The highest average qBHs among occupational risk factors was observed for activities requiring repetitive hand use (6.5 points among the 30 of 45 articles that reported a causal association), substantial exposure to vibration (6.3 points; 14 of 20 articles), and type of occupation (5.6 points; 38 of 53 articles), with the findings being much less consistent.


According to a quantitative analysis of published scientific evidence, the etiology of carpal tunnel syndrome is largely structural, genetic, and biological, with environmental and occupational factors such as repetitive hand use playing a minor and more debatable role. Speculative causal theories should be analyzed through a rigorous approach prior to wide adoption.

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