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In what approximated a controlled clinical trial for efficacy of seatbelts, the Colorado matched pairs study examined 256 crashes meeting the following criteria: driver plus front-seat passenger, one belted (SB) and one nonbelted (NSB) occupant, and at least one occupant injured. Nearly half (119 of 256) of the SB partners escaped injury, while only 16% (41 of 256) of the NSB group were as fortunate. To ascertain a differential effect the 160 pairs discordant for injury were analyzed. The relative odds for injury in the SB group was 0.34 (95% Cl: 0.24, 0.49) of that in the NSB group. Likewise, relative odds for any medical costs in the SB group was reduced to 0.24 (95% Cl: 0.14, 0.43) and for hospitalization to 0.29 (95% Cl: 0.10, 0.80). Sixty-five percent of the SB group had no medical costs in contrast to only 29% of the NSB group. Altogether the NSB group accounted for 76% of the medical costs and 72% of the hospitalizations. This study establishes the effectiveness of seatbelts in reducing nonfatal injuries using epidemiologic, financial, and medical data.