Vol. 102. No. 1
AMERICAN JOURNAL OF EPIDEMIOLOGY
Printed in U.SA.
Copyright © 1975 by The Johns Hopkins University
DRIVING OF MOTOR VEHICLES AS A RISK FACTOR FOR ACUTE HERNIATED LUMBAR INTERVERTEBRAL DISC1 JENNIFER L. KELSEY 2 ' AND ROBERT J. HARDY2 Kelsey. J. L. (Yale U. School of Medicine. New Haven. CT 06510) and R. J . Hardy. Driving of motor vehicles as a risk factor for acute herniated lumbar intervertebral disc. Am J Epidemiol 102:63-73, 1975.—In a case-control study of the epidemiology of acute herniated lumbar intervertebral disc in the New Haven, Connecticut, area, it was found that driving of motor vehicles was associated with an increased risk for developing this disease. It was estimated that men who spend half or more of their time on their job driving a motor vehicle are about three times as likely to develop an acute herniated lumbar disc as those who do not hold such jobs. Persons of either sex who said that they drove a car (either away from work or at work) were more likely to develop an acute herniated lumbar disc than those who did not drive at all. These associations between driving and acute herniated lumbar disc could not be attributed to any confounding variables considered in this study. automobile driving; epidemiologic methods; intervertebral disk displacement; occupations
It is often thought that the low back and sciatic syndrome is a "disease of civilization, a disease of poor physical condition, a disease of the automotive age" (1). However, to our knowledge, it has not been suggested that the driving of automobiles and other motor vehicles is itself involved in the etiology of herniated lumbar disc. In a case-control study of the epidemiology of acute herniated lumbar intervertebral disc in the New Haven, Connecticut, area, the role of possible etiologic agents in the epidemiology of acute herniated lumbar disc was explored. Although driving was not thought of as a risk factor when the
study began, there are several indications from the data that driving plays a role. It is the purpose of this paper to present evidence that driving of motor vehicles may increase the risk for acute herniated lumbar intervertebral disc. In addition, this paper will illustrate a new method (2) of taking into account possible confounding variables in case-control studies in which cases are individually matched to controls on some variables, but in which not all the possible confounding variables were included as matching variables in the study design. METHODS
Received for publication June 11, 1974, and in final form February 3, 1975. 'Supported by USPHS Grant 5-R01-AM-15397 from the National Institute of Arthritis, Metabolism, and Digestive Diseases. 2 Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06510. (Address for reprint requests.) "Supported by Career Development Award 1-K04-NS-70502 from the National Institute of Neurological Diseases and Stroke. The authors would like to thank Dr. Adrian Ostfeld for his suggestions throughout the study and Maryann Bracken, Arlene Finger, and Mary Johnson for assistance with the computer programming.
The overall approach in this study involved comparing characteristics of persons who had acute herniated lumbar intervertebral disc with characteristics of two control groups of persons who were not known to have herniated lumbar disc. Details of the study design are given elsewhere (3), and will be briefly summarized here. Cases. Cases were persons in the age group 20-64 living in the New Haven 63
64
KELSEY AND HARDY
Standard Metropolitan Statistical Area who had lumbo-sacral x-rays taken at all three of the hospitals in the area and at the office of two of the private radiologists in New Haven during the period June, 1971 to May, 1973. X-rays alone are of course of limited value in diagnosing herniated discs, but the assumption was made that most people with low back or sciatic pain would have lumbo-sacral x-rays taken, so that many of those with acute herniated lumbar disc would be among these patients. The people having low back x-rays were interviewed within a few weeks of the time the x-rays were taken and their medical records were reviewed to determine which ones were likely to have acute herniated lumbar discs. During the interview they were asked about their symptoms and were given a few simple diagnostic tests by the interviewers. Among the tests was the straight leg raising test; this was usually done with the patient seated on the edge of a table with his legs dangling, as suggested by Caillet (4), and was considered positive if the pain in the low back or along the sciatic nerve was increased when the leg was slowly extended below the knee. Subsequently the medical records of those whose symptoms and signs were consistent with a herniated disc were reviewed: the radiologists' reports were used to exclude persons with other conditions which could cause the same symptoms and signs (e.g., spondylolisthesis and tumors). The surgeons' reports were abstracted for those who had undergone surgery; and information on the straight leg raising test and other diagnostic tests was recorded in instances in which the patient was not interviewed until after surgery or in which the patient could not be located and interviewed until more than a few weeks had elapsed since he sought medical care. Using the information obtained during the interview and from the medical records, the following diagnostic criteria were
applied: 1) surgical cases: those in which all of the following three criteria were fulfilled: a) the surgeon stated on the hospital chart that he saw the herniated disc during surgery (the descriptions "ruptured," "free fragments," "herniated," "prolapsed," "bulging," and "extruded" are included, but not disc degeneration without evidence of nerve root involvement. The one patient whose medical record indicated that the herniated disc was seen at surgery but who did not have symptoms consistent with a herniated disc is not included as a case); b) the patient gave evidence in his answers to the questionnaire that his pain was distributed along the sciatic nerve; and c) the patient had a positive straight leg raising test and/or the symptoms of increased pain in the low back or along the sciatic nerve when stretching or extending his leg from a sitting position and/or the symptoms of increased pain along the sciatic nerve when coughing or sneezing. 2) probable cases: similar to the surgical except that the herniation need not have been observed at surgery. Included were cases in which the sciatic pain was felt in both the thigh and lower leg and cases in which there was sciatic pain in part of the leg and numbness in another part. 3) possible cases: differed from the probable in that the sciatic pain was only in the thigh or the lower leg but not in both. Also, if the leg was numb so that the distribution of leg pain was unknown, but straight leg raising brought about an increase of pain in the low back, the person was classified as a possible case. Only cases who had recently acquired symptoms of the disease were wanted for the case-control comparison; therefore, persons who had previously had herniated lumbar disc or other serious back problems and persons who had experienced symptoms of herniated disc for more than a year prior to the time they were interviewed were excluded.
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
Controls. The first control group was one in which controls were individually matched to cases. Each surgical, probable, and possible case was matched to the next person of the same sex and of about the same age who was admitted to the same hospital service or to the same radiologist's office for a condition not related to the spine. Emergency room patients were matched within two years of age in two hospitals and within three years of age in the other hospital; the ages of all others were matched within ten years. Persons who would have been classified as surgical, probable, or possible cases or who had previously had a herniated disc or chronic low back pain could not serve as controls. Also excluded as controls were persons who said that they had symptoms of the condition for which they sought medical care for more than one year, so that, as with the cases, they had recently acquired their disease. Persons selected as controls who subsequently had to be excluded were replaced by another person of about the same age and of the same sex admitted to the appropriate hospital service. The second control group was composed of persons who had low back x-rays taken during the period June, 1971, to May, 1973, and were thus interviewed in the course of finding cases, but who were not classified as surgical, probable, or possible cases and who had had their symptoms for less than one year. Since different types of people tended to use the various hospital services, comparisons of these cases and unmatched controls were made in seven separate relatively homogeneous groups for males and six groups for females according to the hospital service: Yale-New Haven Hospital neurosurgical and orthopedic in-patients; Hospital of St. Raphael neurosurgical and orthopedic in-patients; Hospital of St. Raphael emergency room patients; Yale-New Haven Hospital emergency room patients; all other Yale-New Haven and St. Raphael patients; private radiologists' patients;
65
and, for males only, all Veterans Administration Hospital patients. Fourfold tables resulting from these separate comparisons were then combined by the Mantel-Hae.izel (5) procedure so that overall tests of significance could be applied and relative risks estimated. The age distributions of cases and controls in each group were very similar, so they did not have to be compared in separate age groups. Interviewing. The same questionnaire and diagnostic tests were administered by carefully trained non-medical interviewers to all cases and controls. Interviewing was generally done in the homes of the subjects, although when feasible they were interviewed in the hospital. The overall response rate was 79 per cent for persons having low back x-rays and 77 per cent for matched controls. Information on driving of motor vehicles was obtained from two sections of the questionnaire. One of these sections concerned occupational history. Respondents were asked about each job which they held for at least a year since they left school, including among other things what the job was; whether they sat none of the time; a little of the time, half the time, most of the time, or all of the time; and if they sat half the time or more, what kind of chair they usually sat in. Therefore, the specific job that a person held often indicated whether driving was involved and the question about the type of chair gave the respondent the opportunity to say that he sat in a motor vehicle seat when this was the appropriate answer. In another section of the questionnaire, each respondent was asked, "Do you drive a car?" and then was asked the make, model, and year of the car he usually drove. The original purpose of this question had been to see if there was a possible excess risk for herniated lumbar disc among drivers of small cars. Although small cars were not associated with an excess risk (in fact, if anything, they were slightly protective), cases and controls dif-
66
KELSEY AND HARDY
fered significantly in their answers to the question, "Do you drive a car?" Numbers of Cases and Controls. A total of 217 pairs (89 females, 128 males) was obtained for the comparison of cases and matched controls. For the analysis of cases and unmatched controls, there were 223 cases (91 females, 132 males; matched controls could not be obtained for six of the cases seen by private radiologists because of problems related to confidentiality of names of persons seeking medical care from private physicians) and 494 controls (225 females, 269 males). A detailed description of the demographic characteristics of these cases is given elsewhere (3). The highest frequency of new cases occurred in the age group 30-39 years, although there were some cases throughout the 20-64 year age range used in this study. Seventy-eight per cent of the cases were white, 63 per cent had graduated from high school, and 59 per cent lived in the suburbs. Persons were considered city residents if they lived in New Haven; all others were classified as suburban residents. RESULTS
TABLE 1
Male cases and matched controls according to whether they had a job in which they sat half the time or more in a motor vehicle (V) or did not have a job in which they sat half the time or more in a motor vehicle (V) at the time they developed their symptoms, by category of case* No. of pairs with Category
Surgical Probable Possible All cases
CaseV CaseV CaseV CaseV Control Control Control Control V V .V 0 0 0 0
6 8 8 22
4 2 2 8
Total 62 39 27 128
52 29 17 98
* Relative risk = 2.75. x . 2 = 5-633, p < .02. TABLE 2
Proportion of male cases and unmatched controls who had a job in which they sat half the time or more in a motor vehicle, by hospital service* Cases
No.
Proportion with job driving motor vehicle
55
0.145
27
0.037
22
0.227
21
0
Hospital service
Yale-New Haven inpatients St. Raphael in-patients Yale-New Haven emergency room patients St. Raphael emergency room patients Other Yale and St. Raphael patients Private radiologists' patients Veterans Administration patients
Controls
No
'
Proportion with job driving motor vehicle
Driving on Job. The first indication that 17 0.235 81 0.049 driving is involved in the epidemiology of acute herniated lumbar disc comes from the occupational histories of male cases 14 0.143 75 0.133 and controls. Table 1 considers the occupation at the time the symptoms began for 6 0.167 13 0.231 the cases and matched controls; there are 22 pairs in which the case had a job in 4 0.250 13 0.154 which he spent half or more of the time sitting in a motor vehicle and the control 14 0.143 39 0.052 did not, compared to 8 pairs in which the control sat half or more of the time on the job driving a motor vehicle and the case did *X2 test of association calculated by Mantel-Haennot. This difference is statistically signifi- zel procedure: xi2 = 8.993, p < .01, estimate of cant (p < .02), and leads to an estimate of relative risk = 3.14. relative risk of 2.75. When cases are compared to unmatched controls (table 2), in job in the seat of a motor vehicle is greater all groups except group V (in which the than the proportion of controls; the estinumbers are small), the proportion of cases mate of relative risk in the overall comparispending half or more of their time on their son, 3.14 (p < .01), is quite close to the
67
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
estimate for the cases and matched controls. The most frequently mentioned occupation among those whose jobs involved sitting half or more of the time in a motor vehicle was truck driver. In table 3, cases and matched controls are compared according to whether they stated that their occupation was a truck driver (regardless of whether they spent half or more of their time driving the truck). It may be seen that the tendency for more cases than controls to be truck drivers is statistically significant (p < .02); in fact, the calculation of relative risk leads to the estimate that truck drivers are almost five times more likely to develop an acute herniated lumbar disc than males who are not truck drivers. When cases and unmatched controls are compared (table 4), the relative risk is estimated to be 2.26 (p < .02); here, only those truck drivers whose job involved sitting half the time or more are compared. Other occupational groups which seemed to be at excess risk but which were not represented in large enough numbers to be considered separately were police squad car drivers and salesmen who spent half or more of their time on the job driving a motor vehicle. Consideration was also given to whether these respondents had ever had a job in TABLE 3
Male cases and matched controls according to whether their job at the time they developed their symptoms was as a truck driver (T)* or not a truck driver (T), by category of caset No. of pairs with Category CaseT CaseT CaseT CaseT of case Control Control Control Control T T T T
Surgical Probable Possible Total
1
0 0 1
8 2 4 14
1
1 1 3
52 36 22 110
Total 62 39 27 128
* Includes as truck drivers all those who stated that their job was truck driver. t Relative risk = 4.67. Xl 2 = 5.882, p < .02.
TABLE 4
Proportion of male cases and unmatched controls whose job at the time their symptoms developed was as a truck driver.* by hospital serviced Cases Hospital Service No.
Yale-New Haven in- 55 patients St. Raphael in-pa22 tients Yale-New Haven 17 emergency room patients 14 St. Raphael emergency room patients Other Yale and St. 6 Raphael patients Private radiologists' 4 patients 14 Veterans Administration patients
Controls
Proportion truck drivers
No.
Proportion truck drivers
0.091
27
0.037
0.136
21
0
0.176
81
0.049
0.071
75
0.107
0
13
0.231
0.250
13
0
0.071
39
0.026
* Includes as truck drivers those who were truck drivers and who spent half or more of their time on their job sitting in truck seat. t x2 t e s t °f association calculated by Mantel-Haenzel procedure: x2 = 6.016, p < .02, estimate of relative risk = 2.26.
which they spent half or more of their time sitting in a motor vehicle or had ever had a job as a truck driver (for one year or more). Comparisons similar to those given above were made, and, although not shown here, indicate that when cases are compared to matched controls, a male who has ever had a job in which he sat half or more of the time driving a motor vehicle is 2.13 times more likely to develop an acute herniated lumbar disc than someone who has not. When cases are compared to unmatched controls, those who have had a job in which they drove half or more of the time are 1.82 times more likely to develop an acute herniated lumbar disc than those who have not had such a job. A male who has ever been a truck driver (regardless of whether he sat in the truck half the time or more) is estimated to be 2.86 times more likely to
68
KELSEY AND HARDY
develop an acute herniated disc than a male who has never been a truck driver when cases are compared to matched controls, and 1.59 times more likely when cases are compared to unmatched controls (comparing only truck drivers who sat half the time or more). Other Driving. Next, consideration is given to the answers of cases and controls to the question, "Do you drive a car?" Table 5 shows that in the comparison of cases and matched controls, both male and female cases were more likely to say that they drove a car than were their matched controls. The estimate of relative risk indicates that people who drive cars are more than twice as likely to develop acute herniated lumbar intervertebral disc as people who do not drive cars (p < .01). Among cases and unmatched controls, there were again more cases who said that they drove than controls, but the relative risk, 1.29, was somewhat less than for the cases and matched controls and did not reach statistical significance. Effects of Confounding Variables. Thus, the data quite consistently point to a relationship between driving of motor vehicles and the development of acute herniated lumbar disc. However, since drivers and non-drivers are different in various other respects, the question may be raised as to whether the association with driving is really attributable to other characteristics of persons who drive. Among such characteristics would be sex, age, race, educational status, place of residence, and body build. To our knowledge, in case-control studies in which controls are individually matched to cases, no satisfactory method has previously been described for taking into account possible confounding variables which were not included as matching variables in the study design. A new method, described in detail elsewhere (2), is used to determine the possible relevance of these potential confounding variables.
TABLE 5
Comparison of cases and matched controls according to whether they drive a car (D) or do not drive a car (D), by sex and category of case* No. of pairs with Sex and category of case
Males Surgical Probable Possible All males Females Surgical Probable Possible All females Total, both sexes
Case D Control D
Case Case Case D D D Con- Con- Control D trol D trol D
Total
51 28 25 104
10 4 2 16
1 5 0 6
0 2 0 2
62 39 27 128
16 16 8 40 144
5 15 5 25 41
4 6 3 13 19
4 6 1 11 13
29 43 17 89 217
•Relative risk = 2.16. X i 2 = 7.350, p < .01.
Since sex and age were matching variables, these will not be considered further. The racial and social class distributions (3), as well as the average weight of cases and controls were about the same; it is therefore unlikely that these variables can explain the difference in the driving status of cases and controls. However, cases were significantly more likely to be from the suburbs than controls (3), so it is possible that living in the suburbs accounts for the association between driving and herniated lumbar disc. In other words, people who live in the suburbs could be more prone to acute herniated lumbar disc than those who live in the city for reasons other than their tendency to drive, and because of the high correlation between driving and suburban residence, it appears that driving is associated with acute herniated disc. Alternatively, the association between suburban residence and herniated lumbar disc could be explained at least in part by the tendency of suburban residents to drive. Thus, the questions which need to be answered are, first, what is the relative risk for acute herniated lumbar disc for drivers compared
69
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
to non-drivers, holding place of residence constant, and, second, what is the relative risk for acute herniated lumbar disc for suburban residents compared to urban residents, holding driving status constant. Table 6, in which both sexes are combined, presents the case-control pairs according to whether or not each member of the pair drives and according to whether each member of the pair lives in the suburbs or the city. From combining the appropriate cells it can be seen that the simple relative risk for drivers compared to non-drivers is 41/19 = 2.16 (x2 = 7.350, p < .01), and for suburban residents compared to urban residents, 57/37 = 1.54 (x2 = 3.840, p = .05). To estimate the partial effects of driving and place of residence a multiple regression approach to the analysis of matched casecontrol studies is used. The model is the multiple, logistic model P(D) = {1 + exp [- (a + 0lXl + 02X,)]}-1 (1) where P(D) denotes the risk of disease; *i is 1 if the individual drives and 0 if he does not drive; x2 is 1 if the indivdual is a suburban resident and 0 if he is a city
resident. It is well known that the P(D), the absolute risk of disease in the population, cannot be estimated in a case-control study, but that the relative odds can be estimated (which of course approximates the relative risk when the incidence of the disease is low). Likewise, the parameters /?i and 0t can be estimated in a case-control study, and "adjusted" or "partial" relative odds, exp^S,) and exp(/32), obtained. Before describing the procedure by which 0, and /32 can be estimated we note that the odds \P(D)/[1 - P(D)]\ = 0 r^rf* where 0 = exp(a), r, = exp(/8,) and r2 = exp(/32). The parameter r, is the relative increase in the odds of developing disease associated with driving when place of residence is held constant. Similarly, r2 is the relative increase in the odds of developing disease for suburban residents when driving status is held constant. The data in table 6 can be used to make preliminary estimates of r, and r2 by computing the ratios of the symmetric off-diagonal cells. The ratios (2 + 0.5)/(0 + 0.5) and (32 + 0.5)/(29 + 0.5) are estimates of r2; the ratios (14 + 0.5)/(10 + 0.5) and (4 + 0.5)/(l + 0.5) are estimates of rt. (The quantity 0.5 is added to each frequency to
TABLE 6
Cases and matched controls according to whether they drive (D) or do not drive (D) and whether they live in the suburbs (S) or city (S). both sexes and all categories of cases combined Controls
n
D
s Cases
D S S D s
s
Total
63 29 (26.7) 1(1.7) 7 (8.3) 100
Total
S
S
s
32 (34.4)* 20 1 (0.8) 10 (8.2)
4 (3.3) 1(1.2) 2 0 (0.9)
22 (20.7) 14 (15.8) 2(1.1) 9
121 64 6 26
47
217
63
Estimated "simple" relative risk for drivers compared to non-drivers = 2.16 (p < .01). Estimated "adjusted" relative risk for drivers, holding constant place of residence = 1.93 (p = .025). Estimated "simple" relative risk for suburban residents compared to city residents = 1.54 (p = .05). Estimated "adjusted" relative risk for suburban residents, holding constant driving status = 1.30 (p = .25). * Numbers outside of parentheses are observed frequencies; numbers within parentheses denote expected values based on multiple logistic model described in text.
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KELSEY AND HARDY
reduce the bias in the estimate when the frequencies are small.) These are pairs alike in the sense that they are matched for driving status or place of residence, respectively. The ratio (22 + 0.5)/(7 + 0.5) is an estimate of r{r2 and the ratio (1 + 0.5)/(l + 0.5) is an estimate of rjr2. It is quite common for a table such as table 6 to have some cells with small frequencies. The ratios based on these cells will be subject to considerable random variation and the precision of the ratios will be very poor. Therefore, we do not suggest that they be computed routinely, but recommend that over-all estimates of r^ and r2 be made using the combined data. It is also possible to combine the two separate estimates of r t and r2 to obtain estimates of r, and r2 based on pairs which are "matched" for driving status or place of residence. That is, (34 + 0.5)/(29 + 0.5) = 1.17 is an estimate of r2 and (18 + 0.5)/(ll + 0.5) = 1.61 is an estimate of r,. Each of these estimates may be obtained by combining the appropriate cells in table 6. The cells combined to estimate r, can easily be seen in table 6; the cells used to estimate r^ may be more readily noted if a new table is constructed in which driving status and place of residence are interchanged. These two estimates of r, and r2 are quite easy to compute, but are still not based on all the data. The over-all estimates developed and used here use all of the data and are the maximum likelihood estimates of ri and r2. Details of the maximum likelihood estimation will be given elsewhere (2). Briefly, we let (jc,, x2) and (x,', x2') denote the values of the response variables for the case and control members of a matched pair, respectively. As before, x t , x2 = 0, 1; similarly, i,', x2' = 0, 1. The probability P(x1( x 2 | D)P(xl', x 2 '| D) is the probability of the outcome of the case-control pair, with D denoting the presence of the disease and D denoting the absence of the disease. Apply-
ing the definition of conditional probability it can be shown that P(x1,x2\D)P(xl',x2'\D) 1',
x 2 '| D)P(xlt * + /82(x2 -
x 2 ')]
Hence the parameter a which appears in equation (1) is eliminated by computing the ratios of the symmetric off-diagonal cells. Also, the probability distribution of the integer part of the numerator given the sum of the integer parts of the numerator and denominator is binomial; the data from the six independent binomial distributions are combined to form a joint likelihood function from which the maximum likelihood estimates of rt and r2 are obtained. When this analysis is carried out on the data in table 6 we find that #, = 0.66 with a standard deviation of 0.294 and $ 2 = 0.26 with a standard deviation of 0.226. The partial relative odds are rt = exp($,) = 1.93 and r2 = exp(/32) = 1.30. The effect of driving is still significant (p = 0.025), and the effect of place of residence is no longer significant (p = 0.25). The p-values are obtained by dividing each $ by its standard deviation and treating the resulting statistic as a normal random variable with mean zero and standard deviation one when the hypothesis /3 = 0 is true. The numbers in parentheses in table 6 denote the expected values for each cell based on this multiple logistic model. Comparing the observed and expected values, x 2 is 0.701 with 2 degrees of freedom (p = 0.70), indicating that the multiplicative risk model we have used provides a reasonably good fit to the data. In this calculation like pairs were pooled to avoid the small expected values in some of the cells. Maximum likelihood estimates of "adjusted" relative risks were also calculated for drivers, holding constant race and educational status; these adjusted relative
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
risks (2.17 and 2.23, respectively) were almost identical to the simple relative risks. This was as expected since the distributions of cases and matched controls according to race and educational status were very similar. Thus, it does not appear that any of the confounding variables considered here can explain the association between driving and acute herniated lumbar disc. DISCUSSION
Some of the limitations of this study have been discussed previously (3), such as the somewhat disappointing response rate (about 78 per cent), the lack of a control group from the general population, the relatively small sample size, and the tendency of cases to be weighted towards hospitalized patients. To enter this study population, cases had to have sought medical care and had to have been x-rayed, so they constitute a particular subset of all persons with acute herniated lumbar disc. Furthermore, the diagnosis of acute herniated lumbar disc is difficult, as recognized in the establishment of the categories of surgical, probable, and possible cases. In this study, diagnosis was based on symptoms and signs that could be elicited by non-medical but carefully trained interviewers and on information routinely recorded in medical records; the diagnostic criteria were thus particularly appropriate for preliminary epidemiologic research. Undoubtedly some misclassification of cases did occur, both because there were probably some "atypical" cases who were not classified as cases by our criteria and because there might have been a few persons with other conditions which produced the same symptoms and signs as herniated lumbar disc but which were not seen on x-ray. Even among the patients whom we classified as surgical cases, the surgeon might have been reluctant to state on the operative report that he found no disc
71
problem during surgery, although such negative findings at surgery were in fact recorded in the hospital charts of several patients whom we of course did not include in our category of surgical cases. Despite the various limitations of the study, the consistency of the trends among the surgical, probable, and possible cases, and the ability of the risk factors to differentiate between cases and other persons having low back x-rays as well as between cases and matched controls who had no apparent spinal problems, gives one some confidence that persons who probably had acute herniated lumbar disc were in fact to a large extent selected out of the population of persons having low back x-rays. Also, any misclassification that did occur would be expected to make it more difficult to find any true association, so that the real relationship between driving and acute herniated disc could actually be stronger than indicated here. In any event, it is felt that these cases do constitute a large proportion of persons with acute herniated lumbar disc, and it is difficult to see why differences between these cases and controls would not be indicative of differences between persons with and without acute herniated lumbar disc in a more general population. In addition, a particular problem involved in examining driving of motor vehicles as a risk factor was that this was not hypothesized as a risk factor in advance and the questions were not designed specifically to find out in detail about driving. However, since driving stood out clearly as a risk factor in two different parts of the questionnaire, it certainly appears to be more than a chance finding. Driving first appeared as a risk factor when the occupational histories were examined and it was found that persons who spent half or more of their time on their job driving were about three times more likely to develop an acute herniated lumbar disc
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KELSEY AND HARDY
than those who did not have such jobs; this relationship was seen with both control groups, indicating that the association cannot be attributed to unique characteristics of one particular control group. In considering other explanations for the association with driving, it might be thought that truck drivers, who constituted the largest group among those who drive on their job, often do lifting, so that the association with driving on the job is really attributable to lifting. However, neither frequency nor amount of lifting was found to be related to the development of acute herniated lumbar disc (6), so this cannot be the reason. Another possible explanation is that prolonged sitting, regardless of whether it is in a motor vehicle, is detrimental, since length of time spent sitting on the job was in fact found to be associated with acute herniated lumbar disc (6). The relati-'e risk for sitting while driving, however, was nearly twice as high as that for sitting in a chair regardless of the type of chair; in fact, much of the association with sedentary occupations was found to be attributable to occupations in which the sitting was done while driving. It is also possible that lack of physical activity among persons who drive on their job could be related to their increased risk. The indicators of physical activity used in this study, however, showed only a very slight and not statistically significant association between lack of physical activity and herniated lumbar disc, although it must be kept in mind that physical activity is very difficult to assess. Attempts were also made to see if the association between driving other than on the job and acute herniated disc could be attributed to extraneous variables. Because our data indicated that proportionately more drivers than non-drivers are male, young, white, well-educated, suburban residents, smokers, and weigh relatively more, these factors had to be consid-
ered as possible confounding variables. However, since all of these variables except place of residence were either matching variables or were distributed approximately equally in cases and controls, they could not explain the difference. Cases were more likely to come from the suburbs than the controls, but the data suggest that the tendency of suburban residents to drive at least partly accounts for their increased risk for acute herniated disc, and that holding place of residence constant has little effect on the relationship between driving and acute herniated lumbar disc. Thus, we were unable to attribute the association with driving to any confounding variable measured in this study. Further examination of possible confounding variables in future studies is desirable, and it should also be noted that driving is obviously not the only factor involved in the etiology of this condition. The mechanism by which driving would increase the risk for acute herniated lumbar disc cannot be stated with any degree of certainty. Although it is known that sitting puts more pressure on the lumbar discs than standing or lying down (4, 7-8), there has apparently been no experimental work on the effects on the lumbar intervertebral discs of sitting while driving a motor vehicle. Nevertheless, it is not difficult to think of explanations for an adverse effect of driving on the disc. For example, Keegan (7) has pointed out that most motor vehicle seats provide insufficient support for the low back; he has observed that people with low back pain frequently are unable to sit in comfort in automobiles and that they have difficulty straightening their backs on rising despite the purported comfort of the seats. In addition, people while driving generally sit with their legs extended to the floor pedals, rather than flat on the floor, and are subject to continual vibration and to mechanical stress from starting and stopping. It would be useful if experimental studies were undertaken to
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
examine the effects of these potential stresses on the lumbar discs. Finally, it has been observed many times that lumbar disc herniations are most common at the L4 and L5 levels; however, Sprangfort (9) recently noted that whereas a few decades ago L5 herniations were more common than L4 herniations, recent series seem to show that L4 herniations are at least as common as L6 herniations if not more common. In the present study population, the level of the lesion could only be known with certainty for the surgical cases, and the L s and L4 levels were involved with almost equal frequency (3). However, of the six surgical cases who spent at least half of their time on their job driving a motor vehicle, five had L4 herniations. When considering the answers of the surgical cases and matched controls to the question "Do you drive a car?," it was found that the overall difference was almost entirely attributable to those with herniations at the L 4 level. Thus, although based on small numbers, these data give some suggestion that driving is a particularly strong risk factor for herniations at the L 4 level; this would of course be consistent with an increase in the proportion of herniations at the L 4 level over the past
73
years as the amount of driving has increased. This is speculative, however, and is mentioned here only as a suggestion that it be examined in future studies.
REFERENCES
1. Coventry MB: Introduction to symposium, including anatomy, physiology, and epidemiology. J Bone Joint Surg (Am) 50:167-169, 1968 2. Hardy RJ: Unpublished observations 3. Kelsey JL, Ostfeld AM: Demographic characteristics of persons with acute herniated lumbar intervertebral disc. J Chron Dis 28:37-50, 1975 4. Caillet R: Low Back Pain Syndrome. Philadelphia, Davis, 1968 5. Mantel N, Haenzel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719-748, 1959 6. Kelsey JL: An epidemiological study of the relationship between occupations and acute herniated lumbar intervertebral disc. Presented at the International Epidemiological Association Seventh International Scientific Meeting, Brighton, England, August, 1974 7. Keegan JJ: Alterations of the lumbar curve related to posture and seating. J Bone Joint Surg (Am) 35:589-603, 1953 8. Nachemson A: In vivo discometry in lumbar discs with irregular radiograms. Acta Orthop Scand 36:418-434, 1965 9. Spangfort EV: The lumbar disc herniation, a computer-aided analysis of 2,504 operations. Acta Orthop Scand (Suppl) 142:1-95, 1972
AMERICAN JOURNAL OF EPIDEMIOLOGY
Printed in U.SA.
Copyright © 1975 by The Johns Hopkins University
DRIVING OF MOTOR VEHICLES AS A RISK FACTOR FOR ACUTE HERNIATED LUMBAR INTERVERTEBRAL DISC1 JENNIFER L. KELSEY 2 ' AND ROBERT J. HARDY2 Kelsey. J. L. (Yale U. School of Medicine. New Haven. CT 06510) and R. J . Hardy. Driving of motor vehicles as a risk factor for acute herniated lumbar intervertebral disc. Am J Epidemiol 102:63-73, 1975.—In a case-control study of the epidemiology of acute herniated lumbar intervertebral disc in the New Haven, Connecticut, area, it was found that driving of motor vehicles was associated with an increased risk for developing this disease. It was estimated that men who spend half or more of their time on their job driving a motor vehicle are about three times as likely to develop an acute herniated lumbar disc as those who do not hold such jobs. Persons of either sex who said that they drove a car (either away from work or at work) were more likely to develop an acute herniated lumbar disc than those who did not drive at all. These associations between driving and acute herniated lumbar disc could not be attributed to any confounding variables considered in this study. automobile driving; epidemiologic methods; intervertebral disk displacement; occupations
It is often thought that the low back and sciatic syndrome is a "disease of civilization, a disease of poor physical condition, a disease of the automotive age" (1). However, to our knowledge, it has not been suggested that the driving of automobiles and other motor vehicles is itself involved in the etiology of herniated lumbar disc. In a case-control study of the epidemiology of acute herniated lumbar intervertebral disc in the New Haven, Connecticut, area, the role of possible etiologic agents in the epidemiology of acute herniated lumbar disc was explored. Although driving was not thought of as a risk factor when the
study began, there are several indications from the data that driving plays a role. It is the purpose of this paper to present evidence that driving of motor vehicles may increase the risk for acute herniated lumbar intervertebral disc. In addition, this paper will illustrate a new method (2) of taking into account possible confounding variables in case-control studies in which cases are individually matched to controls on some variables, but in which not all the possible confounding variables were included as matching variables in the study design. METHODS
Received for publication June 11, 1974, and in final form February 3, 1975. 'Supported by USPHS Grant 5-R01-AM-15397 from the National Institute of Arthritis, Metabolism, and Digestive Diseases. 2 Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06510. (Address for reprint requests.) "Supported by Career Development Award 1-K04-NS-70502 from the National Institute of Neurological Diseases and Stroke. The authors would like to thank Dr. Adrian Ostfeld for his suggestions throughout the study and Maryann Bracken, Arlene Finger, and Mary Johnson for assistance with the computer programming.
The overall approach in this study involved comparing characteristics of persons who had acute herniated lumbar intervertebral disc with characteristics of two control groups of persons who were not known to have herniated lumbar disc. Details of the study design are given elsewhere (3), and will be briefly summarized here. Cases. Cases were persons in the age group 20-64 living in the New Haven 63
64
KELSEY AND HARDY
Standard Metropolitan Statistical Area who had lumbo-sacral x-rays taken at all three of the hospitals in the area and at the office of two of the private radiologists in New Haven during the period June, 1971 to May, 1973. X-rays alone are of course of limited value in diagnosing herniated discs, but the assumption was made that most people with low back or sciatic pain would have lumbo-sacral x-rays taken, so that many of those with acute herniated lumbar disc would be among these patients. The people having low back x-rays were interviewed within a few weeks of the time the x-rays were taken and their medical records were reviewed to determine which ones were likely to have acute herniated lumbar discs. During the interview they were asked about their symptoms and were given a few simple diagnostic tests by the interviewers. Among the tests was the straight leg raising test; this was usually done with the patient seated on the edge of a table with his legs dangling, as suggested by Caillet (4), and was considered positive if the pain in the low back or along the sciatic nerve was increased when the leg was slowly extended below the knee. Subsequently the medical records of those whose symptoms and signs were consistent with a herniated disc were reviewed: the radiologists' reports were used to exclude persons with other conditions which could cause the same symptoms and signs (e.g., spondylolisthesis and tumors). The surgeons' reports were abstracted for those who had undergone surgery; and information on the straight leg raising test and other diagnostic tests was recorded in instances in which the patient was not interviewed until after surgery or in which the patient could not be located and interviewed until more than a few weeks had elapsed since he sought medical care. Using the information obtained during the interview and from the medical records, the following diagnostic criteria were
applied: 1) surgical cases: those in which all of the following three criteria were fulfilled: a) the surgeon stated on the hospital chart that he saw the herniated disc during surgery (the descriptions "ruptured," "free fragments," "herniated," "prolapsed," "bulging," and "extruded" are included, but not disc degeneration without evidence of nerve root involvement. The one patient whose medical record indicated that the herniated disc was seen at surgery but who did not have symptoms consistent with a herniated disc is not included as a case); b) the patient gave evidence in his answers to the questionnaire that his pain was distributed along the sciatic nerve; and c) the patient had a positive straight leg raising test and/or the symptoms of increased pain in the low back or along the sciatic nerve when stretching or extending his leg from a sitting position and/or the symptoms of increased pain along the sciatic nerve when coughing or sneezing. 2) probable cases: similar to the surgical except that the herniation need not have been observed at surgery. Included were cases in which the sciatic pain was felt in both the thigh and lower leg and cases in which there was sciatic pain in part of the leg and numbness in another part. 3) possible cases: differed from the probable in that the sciatic pain was only in the thigh or the lower leg but not in both. Also, if the leg was numb so that the distribution of leg pain was unknown, but straight leg raising brought about an increase of pain in the low back, the person was classified as a possible case. Only cases who had recently acquired symptoms of the disease were wanted for the case-control comparison; therefore, persons who had previously had herniated lumbar disc or other serious back problems and persons who had experienced symptoms of herniated disc for more than a year prior to the time they were interviewed were excluded.
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
Controls. The first control group was one in which controls were individually matched to cases. Each surgical, probable, and possible case was matched to the next person of the same sex and of about the same age who was admitted to the same hospital service or to the same radiologist's office for a condition not related to the spine. Emergency room patients were matched within two years of age in two hospitals and within three years of age in the other hospital; the ages of all others were matched within ten years. Persons who would have been classified as surgical, probable, or possible cases or who had previously had a herniated disc or chronic low back pain could not serve as controls. Also excluded as controls were persons who said that they had symptoms of the condition for which they sought medical care for more than one year, so that, as with the cases, they had recently acquired their disease. Persons selected as controls who subsequently had to be excluded were replaced by another person of about the same age and of the same sex admitted to the appropriate hospital service. The second control group was composed of persons who had low back x-rays taken during the period June, 1971, to May, 1973, and were thus interviewed in the course of finding cases, but who were not classified as surgical, probable, or possible cases and who had had their symptoms for less than one year. Since different types of people tended to use the various hospital services, comparisons of these cases and unmatched controls were made in seven separate relatively homogeneous groups for males and six groups for females according to the hospital service: Yale-New Haven Hospital neurosurgical and orthopedic in-patients; Hospital of St. Raphael neurosurgical and orthopedic in-patients; Hospital of St. Raphael emergency room patients; Yale-New Haven Hospital emergency room patients; all other Yale-New Haven and St. Raphael patients; private radiologists' patients;
65
and, for males only, all Veterans Administration Hospital patients. Fourfold tables resulting from these separate comparisons were then combined by the Mantel-Hae.izel (5) procedure so that overall tests of significance could be applied and relative risks estimated. The age distributions of cases and controls in each group were very similar, so they did not have to be compared in separate age groups. Interviewing. The same questionnaire and diagnostic tests were administered by carefully trained non-medical interviewers to all cases and controls. Interviewing was generally done in the homes of the subjects, although when feasible they were interviewed in the hospital. The overall response rate was 79 per cent for persons having low back x-rays and 77 per cent for matched controls. Information on driving of motor vehicles was obtained from two sections of the questionnaire. One of these sections concerned occupational history. Respondents were asked about each job which they held for at least a year since they left school, including among other things what the job was; whether they sat none of the time; a little of the time, half the time, most of the time, or all of the time; and if they sat half the time or more, what kind of chair they usually sat in. Therefore, the specific job that a person held often indicated whether driving was involved and the question about the type of chair gave the respondent the opportunity to say that he sat in a motor vehicle seat when this was the appropriate answer. In another section of the questionnaire, each respondent was asked, "Do you drive a car?" and then was asked the make, model, and year of the car he usually drove. The original purpose of this question had been to see if there was a possible excess risk for herniated lumbar disc among drivers of small cars. Although small cars were not associated with an excess risk (in fact, if anything, they were slightly protective), cases and controls dif-
66
KELSEY AND HARDY
fered significantly in their answers to the question, "Do you drive a car?" Numbers of Cases and Controls. A total of 217 pairs (89 females, 128 males) was obtained for the comparison of cases and matched controls. For the analysis of cases and unmatched controls, there were 223 cases (91 females, 132 males; matched controls could not be obtained for six of the cases seen by private radiologists because of problems related to confidentiality of names of persons seeking medical care from private physicians) and 494 controls (225 females, 269 males). A detailed description of the demographic characteristics of these cases is given elsewhere (3). The highest frequency of new cases occurred in the age group 30-39 years, although there were some cases throughout the 20-64 year age range used in this study. Seventy-eight per cent of the cases were white, 63 per cent had graduated from high school, and 59 per cent lived in the suburbs. Persons were considered city residents if they lived in New Haven; all others were classified as suburban residents. RESULTS
TABLE 1
Male cases and matched controls according to whether they had a job in which they sat half the time or more in a motor vehicle (V) or did not have a job in which they sat half the time or more in a motor vehicle (V) at the time they developed their symptoms, by category of case* No. of pairs with Category
Surgical Probable Possible All cases
CaseV CaseV CaseV CaseV Control Control Control Control V V .V 0 0 0 0
6 8 8 22
4 2 2 8
Total 62 39 27 128
52 29 17 98
* Relative risk = 2.75. x . 2 = 5-633, p < .02. TABLE 2
Proportion of male cases and unmatched controls who had a job in which they sat half the time or more in a motor vehicle, by hospital service* Cases
No.
Proportion with job driving motor vehicle
55
0.145
27
0.037
22
0.227
21
0
Hospital service
Yale-New Haven inpatients St. Raphael in-patients Yale-New Haven emergency room patients St. Raphael emergency room patients Other Yale and St. Raphael patients Private radiologists' patients Veterans Administration patients
Controls
No
'
Proportion with job driving motor vehicle
Driving on Job. The first indication that 17 0.235 81 0.049 driving is involved in the epidemiology of acute herniated lumbar disc comes from the occupational histories of male cases 14 0.143 75 0.133 and controls. Table 1 considers the occupation at the time the symptoms began for 6 0.167 13 0.231 the cases and matched controls; there are 22 pairs in which the case had a job in 4 0.250 13 0.154 which he spent half or more of the time sitting in a motor vehicle and the control 14 0.143 39 0.052 did not, compared to 8 pairs in which the control sat half or more of the time on the job driving a motor vehicle and the case did *X2 test of association calculated by Mantel-Haennot. This difference is statistically signifi- zel procedure: xi2 = 8.993, p < .01, estimate of cant (p < .02), and leads to an estimate of relative risk = 3.14. relative risk of 2.75. When cases are compared to unmatched controls (table 2), in job in the seat of a motor vehicle is greater all groups except group V (in which the than the proportion of controls; the estinumbers are small), the proportion of cases mate of relative risk in the overall comparispending half or more of their time on their son, 3.14 (p < .01), is quite close to the
67
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
estimate for the cases and matched controls. The most frequently mentioned occupation among those whose jobs involved sitting half or more of the time in a motor vehicle was truck driver. In table 3, cases and matched controls are compared according to whether they stated that their occupation was a truck driver (regardless of whether they spent half or more of their time driving the truck). It may be seen that the tendency for more cases than controls to be truck drivers is statistically significant (p < .02); in fact, the calculation of relative risk leads to the estimate that truck drivers are almost five times more likely to develop an acute herniated lumbar disc than males who are not truck drivers. When cases and unmatched controls are compared (table 4), the relative risk is estimated to be 2.26 (p < .02); here, only those truck drivers whose job involved sitting half the time or more are compared. Other occupational groups which seemed to be at excess risk but which were not represented in large enough numbers to be considered separately were police squad car drivers and salesmen who spent half or more of their time on the job driving a motor vehicle. Consideration was also given to whether these respondents had ever had a job in TABLE 3
Male cases and matched controls according to whether their job at the time they developed their symptoms was as a truck driver (T)* or not a truck driver (T), by category of caset No. of pairs with Category CaseT CaseT CaseT CaseT of case Control Control Control Control T T T T
Surgical Probable Possible Total
1
0 0 1
8 2 4 14
1
1 1 3
52 36 22 110
Total 62 39 27 128
* Includes as truck drivers all those who stated that their job was truck driver. t Relative risk = 4.67. Xl 2 = 5.882, p < .02.
TABLE 4
Proportion of male cases and unmatched controls whose job at the time their symptoms developed was as a truck driver.* by hospital serviced Cases Hospital Service No.
Yale-New Haven in- 55 patients St. Raphael in-pa22 tients Yale-New Haven 17 emergency room patients 14 St. Raphael emergency room patients Other Yale and St. 6 Raphael patients Private radiologists' 4 patients 14 Veterans Administration patients
Controls
Proportion truck drivers
No.
Proportion truck drivers
0.091
27
0.037
0.136
21
0
0.176
81
0.049
0.071
75
0.107
0
13
0.231
0.250
13
0
0.071
39
0.026
* Includes as truck drivers those who were truck drivers and who spent half or more of their time on their job sitting in truck seat. t x2 t e s t °f association calculated by Mantel-Haenzel procedure: x2 = 6.016, p < .02, estimate of relative risk = 2.26.
which they spent half or more of their time sitting in a motor vehicle or had ever had a job as a truck driver (for one year or more). Comparisons similar to those given above were made, and, although not shown here, indicate that when cases are compared to matched controls, a male who has ever had a job in which he sat half or more of the time driving a motor vehicle is 2.13 times more likely to develop an acute herniated lumbar disc than someone who has not. When cases are compared to unmatched controls, those who have had a job in which they drove half or more of the time are 1.82 times more likely to develop an acute herniated lumbar disc than those who have not had such a job. A male who has ever been a truck driver (regardless of whether he sat in the truck half the time or more) is estimated to be 2.86 times more likely to
68
KELSEY AND HARDY
develop an acute herniated disc than a male who has never been a truck driver when cases are compared to matched controls, and 1.59 times more likely when cases are compared to unmatched controls (comparing only truck drivers who sat half the time or more). Other Driving. Next, consideration is given to the answers of cases and controls to the question, "Do you drive a car?" Table 5 shows that in the comparison of cases and matched controls, both male and female cases were more likely to say that they drove a car than were their matched controls. The estimate of relative risk indicates that people who drive cars are more than twice as likely to develop acute herniated lumbar intervertebral disc as people who do not drive cars (p < .01). Among cases and unmatched controls, there were again more cases who said that they drove than controls, but the relative risk, 1.29, was somewhat less than for the cases and matched controls and did not reach statistical significance. Effects of Confounding Variables. Thus, the data quite consistently point to a relationship between driving of motor vehicles and the development of acute herniated lumbar disc. However, since drivers and non-drivers are different in various other respects, the question may be raised as to whether the association with driving is really attributable to other characteristics of persons who drive. Among such characteristics would be sex, age, race, educational status, place of residence, and body build. To our knowledge, in case-control studies in which controls are individually matched to cases, no satisfactory method has previously been described for taking into account possible confounding variables which were not included as matching variables in the study design. A new method, described in detail elsewhere (2), is used to determine the possible relevance of these potential confounding variables.
TABLE 5
Comparison of cases and matched controls according to whether they drive a car (D) or do not drive a car (D), by sex and category of case* No. of pairs with Sex and category of case
Males Surgical Probable Possible All males Females Surgical Probable Possible All females Total, both sexes
Case D Control D
Case Case Case D D D Con- Con- Control D trol D trol D
Total
51 28 25 104
10 4 2 16
1 5 0 6
0 2 0 2
62 39 27 128
16 16 8 40 144
5 15 5 25 41
4 6 3 13 19
4 6 1 11 13
29 43 17 89 217
•Relative risk = 2.16. X i 2 = 7.350, p < .01.
Since sex and age were matching variables, these will not be considered further. The racial and social class distributions (3), as well as the average weight of cases and controls were about the same; it is therefore unlikely that these variables can explain the difference in the driving status of cases and controls. However, cases were significantly more likely to be from the suburbs than controls (3), so it is possible that living in the suburbs accounts for the association between driving and herniated lumbar disc. In other words, people who live in the suburbs could be more prone to acute herniated lumbar disc than those who live in the city for reasons other than their tendency to drive, and because of the high correlation between driving and suburban residence, it appears that driving is associated with acute herniated disc. Alternatively, the association between suburban residence and herniated lumbar disc could be explained at least in part by the tendency of suburban residents to drive. Thus, the questions which need to be answered are, first, what is the relative risk for acute herniated lumbar disc for drivers compared
69
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
to non-drivers, holding place of residence constant, and, second, what is the relative risk for acute herniated lumbar disc for suburban residents compared to urban residents, holding driving status constant. Table 6, in which both sexes are combined, presents the case-control pairs according to whether or not each member of the pair drives and according to whether each member of the pair lives in the suburbs or the city. From combining the appropriate cells it can be seen that the simple relative risk for drivers compared to non-drivers is 41/19 = 2.16 (x2 = 7.350, p < .01), and for suburban residents compared to urban residents, 57/37 = 1.54 (x2 = 3.840, p = .05). To estimate the partial effects of driving and place of residence a multiple regression approach to the analysis of matched casecontrol studies is used. The model is the multiple, logistic model P(D) = {1 + exp [- (a + 0lXl + 02X,)]}-1 (1) where P(D) denotes the risk of disease; *i is 1 if the individual drives and 0 if he does not drive; x2 is 1 if the indivdual is a suburban resident and 0 if he is a city
resident. It is well known that the P(D), the absolute risk of disease in the population, cannot be estimated in a case-control study, but that the relative odds can be estimated (which of course approximates the relative risk when the incidence of the disease is low). Likewise, the parameters /?i and 0t can be estimated in a case-control study, and "adjusted" or "partial" relative odds, exp^S,) and exp(/32), obtained. Before describing the procedure by which 0, and /32 can be estimated we note that the odds \P(D)/[1 - P(D)]\ = 0 r^rf* where 0 = exp(a), r, = exp(/8,) and r2 = exp(/32). The parameter r, is the relative increase in the odds of developing disease associated with driving when place of residence is held constant. Similarly, r2 is the relative increase in the odds of developing disease for suburban residents when driving status is held constant. The data in table 6 can be used to make preliminary estimates of r, and r2 by computing the ratios of the symmetric off-diagonal cells. The ratios (2 + 0.5)/(0 + 0.5) and (32 + 0.5)/(29 + 0.5) are estimates of r2; the ratios (14 + 0.5)/(10 + 0.5) and (4 + 0.5)/(l + 0.5) are estimates of rt. (The quantity 0.5 is added to each frequency to
TABLE 6
Cases and matched controls according to whether they drive (D) or do not drive (D) and whether they live in the suburbs (S) or city (S). both sexes and all categories of cases combined Controls
n
D
s Cases
D S S D s
s
Total
63 29 (26.7) 1(1.7) 7 (8.3) 100
Total
S
S
s
32 (34.4)* 20 1 (0.8) 10 (8.2)
4 (3.3) 1(1.2) 2 0 (0.9)
22 (20.7) 14 (15.8) 2(1.1) 9
121 64 6 26
47
217
63
Estimated "simple" relative risk for drivers compared to non-drivers = 2.16 (p < .01). Estimated "adjusted" relative risk for drivers, holding constant place of residence = 1.93 (p = .025). Estimated "simple" relative risk for suburban residents compared to city residents = 1.54 (p = .05). Estimated "adjusted" relative risk for suburban residents, holding constant driving status = 1.30 (p = .25). * Numbers outside of parentheses are observed frequencies; numbers within parentheses denote expected values based on multiple logistic model described in text.
70
KELSEY AND HARDY
reduce the bias in the estimate when the frequencies are small.) These are pairs alike in the sense that they are matched for driving status or place of residence, respectively. The ratio (22 + 0.5)/(7 + 0.5) is an estimate of r{r2 and the ratio (1 + 0.5)/(l + 0.5) is an estimate of rjr2. It is quite common for a table such as table 6 to have some cells with small frequencies. The ratios based on these cells will be subject to considerable random variation and the precision of the ratios will be very poor. Therefore, we do not suggest that they be computed routinely, but recommend that over-all estimates of r^ and r2 be made using the combined data. It is also possible to combine the two separate estimates of r t and r2 to obtain estimates of r, and r2 based on pairs which are "matched" for driving status or place of residence. That is, (34 + 0.5)/(29 + 0.5) = 1.17 is an estimate of r2 and (18 + 0.5)/(ll + 0.5) = 1.61 is an estimate of r,. Each of these estimates may be obtained by combining the appropriate cells in table 6. The cells combined to estimate r, can easily be seen in table 6; the cells used to estimate r^ may be more readily noted if a new table is constructed in which driving status and place of residence are interchanged. These two estimates of r, and r2 are quite easy to compute, but are still not based on all the data. The over-all estimates developed and used here use all of the data and are the maximum likelihood estimates of ri and r2. Details of the maximum likelihood estimation will be given elsewhere (2). Briefly, we let (jc,, x2) and (x,', x2') denote the values of the response variables for the case and control members of a matched pair, respectively. As before, x t , x2 = 0, 1; similarly, i,', x2' = 0, 1. The probability P(x1( x 2 | D)P(xl', x 2 '| D) is the probability of the outcome of the case-control pair, with D denoting the presence of the disease and D denoting the absence of the disease. Apply-
ing the definition of conditional probability it can be shown that P(x1,x2\D)P(xl',x2'\D) 1',
x 2 '| D)P(xlt * + /82(x2 -
x 2 ')]
Hence the parameter a which appears in equation (1) is eliminated by computing the ratios of the symmetric off-diagonal cells. Also, the probability distribution of the integer part of the numerator given the sum of the integer parts of the numerator and denominator is binomial; the data from the six independent binomial distributions are combined to form a joint likelihood function from which the maximum likelihood estimates of rt and r2 are obtained. When this analysis is carried out on the data in table 6 we find that #, = 0.66 with a standard deviation of 0.294 and $ 2 = 0.26 with a standard deviation of 0.226. The partial relative odds are rt = exp($,) = 1.93 and r2 = exp(/32) = 1.30. The effect of driving is still significant (p = 0.025), and the effect of place of residence is no longer significant (p = 0.25). The p-values are obtained by dividing each $ by its standard deviation and treating the resulting statistic as a normal random variable with mean zero and standard deviation one when the hypothesis /3 = 0 is true. The numbers in parentheses in table 6 denote the expected values for each cell based on this multiple logistic model. Comparing the observed and expected values, x 2 is 0.701 with 2 degrees of freedom (p = 0.70), indicating that the multiplicative risk model we have used provides a reasonably good fit to the data. In this calculation like pairs were pooled to avoid the small expected values in some of the cells. Maximum likelihood estimates of "adjusted" relative risks were also calculated for drivers, holding constant race and educational status; these adjusted relative
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
risks (2.17 and 2.23, respectively) were almost identical to the simple relative risks. This was as expected since the distributions of cases and matched controls according to race and educational status were very similar. Thus, it does not appear that any of the confounding variables considered here can explain the association between driving and acute herniated lumbar disc. DISCUSSION
Some of the limitations of this study have been discussed previously (3), such as the somewhat disappointing response rate (about 78 per cent), the lack of a control group from the general population, the relatively small sample size, and the tendency of cases to be weighted towards hospitalized patients. To enter this study population, cases had to have sought medical care and had to have been x-rayed, so they constitute a particular subset of all persons with acute herniated lumbar disc. Furthermore, the diagnosis of acute herniated lumbar disc is difficult, as recognized in the establishment of the categories of surgical, probable, and possible cases. In this study, diagnosis was based on symptoms and signs that could be elicited by non-medical but carefully trained interviewers and on information routinely recorded in medical records; the diagnostic criteria were thus particularly appropriate for preliminary epidemiologic research. Undoubtedly some misclassification of cases did occur, both because there were probably some "atypical" cases who were not classified as cases by our criteria and because there might have been a few persons with other conditions which produced the same symptoms and signs as herniated lumbar disc but which were not seen on x-ray. Even among the patients whom we classified as surgical cases, the surgeon might have been reluctant to state on the operative report that he found no disc
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problem during surgery, although such negative findings at surgery were in fact recorded in the hospital charts of several patients whom we of course did not include in our category of surgical cases. Despite the various limitations of the study, the consistency of the trends among the surgical, probable, and possible cases, and the ability of the risk factors to differentiate between cases and other persons having low back x-rays as well as between cases and matched controls who had no apparent spinal problems, gives one some confidence that persons who probably had acute herniated lumbar disc were in fact to a large extent selected out of the population of persons having low back x-rays. Also, any misclassification that did occur would be expected to make it more difficult to find any true association, so that the real relationship between driving and acute herniated disc could actually be stronger than indicated here. In any event, it is felt that these cases do constitute a large proportion of persons with acute herniated lumbar disc, and it is difficult to see why differences between these cases and controls would not be indicative of differences between persons with and without acute herniated lumbar disc in a more general population. In addition, a particular problem involved in examining driving of motor vehicles as a risk factor was that this was not hypothesized as a risk factor in advance and the questions were not designed specifically to find out in detail about driving. However, since driving stood out clearly as a risk factor in two different parts of the questionnaire, it certainly appears to be more than a chance finding. Driving first appeared as a risk factor when the occupational histories were examined and it was found that persons who spent half or more of their time on their job driving were about three times more likely to develop an acute herniated lumbar disc
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KELSEY AND HARDY
than those who did not have such jobs; this relationship was seen with both control groups, indicating that the association cannot be attributed to unique characteristics of one particular control group. In considering other explanations for the association with driving, it might be thought that truck drivers, who constituted the largest group among those who drive on their job, often do lifting, so that the association with driving on the job is really attributable to lifting. However, neither frequency nor amount of lifting was found to be related to the development of acute herniated lumbar disc (6), so this cannot be the reason. Another possible explanation is that prolonged sitting, regardless of whether it is in a motor vehicle, is detrimental, since length of time spent sitting on the job was in fact found to be associated with acute herniated lumbar disc (6). The relati-'e risk for sitting while driving, however, was nearly twice as high as that for sitting in a chair regardless of the type of chair; in fact, much of the association with sedentary occupations was found to be attributable to occupations in which the sitting was done while driving. It is also possible that lack of physical activity among persons who drive on their job could be related to their increased risk. The indicators of physical activity used in this study, however, showed only a very slight and not statistically significant association between lack of physical activity and herniated lumbar disc, although it must be kept in mind that physical activity is very difficult to assess. Attempts were also made to see if the association between driving other than on the job and acute herniated disc could be attributed to extraneous variables. Because our data indicated that proportionately more drivers than non-drivers are male, young, white, well-educated, suburban residents, smokers, and weigh relatively more, these factors had to be consid-
ered as possible confounding variables. However, since all of these variables except place of residence were either matching variables or were distributed approximately equally in cases and controls, they could not explain the difference. Cases were more likely to come from the suburbs than the controls, but the data suggest that the tendency of suburban residents to drive at least partly accounts for their increased risk for acute herniated disc, and that holding place of residence constant has little effect on the relationship between driving and acute herniated lumbar disc. Thus, we were unable to attribute the association with driving to any confounding variable measured in this study. Further examination of possible confounding variables in future studies is desirable, and it should also be noted that driving is obviously not the only factor involved in the etiology of this condition. The mechanism by which driving would increase the risk for acute herniated lumbar disc cannot be stated with any degree of certainty. Although it is known that sitting puts more pressure on the lumbar discs than standing or lying down (4, 7-8), there has apparently been no experimental work on the effects on the lumbar intervertebral discs of sitting while driving a motor vehicle. Nevertheless, it is not difficult to think of explanations for an adverse effect of driving on the disc. For example, Keegan (7) has pointed out that most motor vehicle seats provide insufficient support for the low back; he has observed that people with low back pain frequently are unable to sit in comfort in automobiles and that they have difficulty straightening their backs on rising despite the purported comfort of the seats. In addition, people while driving generally sit with their legs extended to the floor pedals, rather than flat on the floor, and are subject to continual vibration and to mechanical stress from starting and stopping. It would be useful if experimental studies were undertaken to
DRIVING AS A RISK FACTOR IN HERNIATED LUMBAR DISC
examine the effects of these potential stresses on the lumbar discs. Finally, it has been observed many times that lumbar disc herniations are most common at the L4 and L5 levels; however, Sprangfort (9) recently noted that whereas a few decades ago L5 herniations were more common than L4 herniations, recent series seem to show that L4 herniations are at least as common as L6 herniations if not more common. In the present study population, the level of the lesion could only be known with certainty for the surgical cases, and the L s and L4 levels were involved with almost equal frequency (3). However, of the six surgical cases who spent at least half of their time on their job driving a motor vehicle, five had L4 herniations. When considering the answers of the surgical cases and matched controls to the question "Do you drive a car?," it was found that the overall difference was almost entirely attributable to those with herniations at the L 4 level. Thus, although based on small numbers, these data give some suggestion that driving is a particularly strong risk factor for herniations at the L 4 level; this would of course be consistent with an increase in the proportion of herniations at the L 4 level over the past
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years as the amount of driving has increased. This is speculative, however, and is mentioned here only as a suggestion that it be examined in future studies.
REFERENCES
1. Coventry MB: Introduction to symposium, including anatomy, physiology, and epidemiology. J Bone Joint Surg (Am) 50:167-169, 1968 2. Hardy RJ: Unpublished observations 3. Kelsey JL, Ostfeld AM: Demographic characteristics of persons with acute herniated lumbar intervertebral disc. J Chron Dis 28:37-50, 1975 4. Caillet R: Low Back Pain Syndrome. Philadelphia, Davis, 1968 5. Mantel N, Haenzel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719-748, 1959 6. Kelsey JL: An epidemiological study of the relationship between occupations and acute herniated lumbar intervertebral disc. Presented at the International Epidemiological Association Seventh International Scientific Meeting, Brighton, England, August, 1974 7. Keegan JJ: Alterations of the lumbar curve related to posture and seating. J Bone Joint Surg (Am) 35:589-603, 1953 8. Nachemson A: In vivo discometry in lumbar discs with irregular radiograms. Acta Orthop Scand 36:418-434, 1965 9. Spangfort EV: The lumbar disc herniation, a computer-aided analysis of 2,504 operations. Acta Orthop Scand (Suppl) 142:1-95, 1972
