|Sciatica: Studies of symptoms, genetic factors, and treatment with periradicular infiltration|
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Preliminary calculations showed a need for 68 patients in both (steroid and saline) treatment groups (α=0.90, two-sided β =0.05). The calculations were made for leg pain (the primary outcome) on the VAS scale, using a clinically significant difference between the groups with a rating of 15 mm and assuming a standard deviation of 15%. After adjusting for a 20 % loss to follow-up evaluation, 80 persons were enrolled for both groups.
Kappa statistics were used to establish interobserver (reader 1 vs. reader 2) and intraobserver (reader 1 vs. reread of reader 1) reliabilities of the various MRI findings (Altman 1991). Interobserver and intraobserver kappa values for the various MRI findings showed mostly moderate to substantial agreement (I, table 1). The interobserver kappa value for TLS was 0.71 (substantial agreement) and the intraobserver value 1.0 (perfect agreement)
The intercorrelations of the different diagnostic tests (clinical tests and MRI findings), demographic characteristics, and sciatic symptoms were investigated by Spearman correlation analysis. The significances were tested with the Pearson chi-square and Fisher’s exact test (2x2 tables) for nominal and ordinal variables or with Student’s t-test and Kruskal-Wallis ANOVA (depending on the skewness of the variable in question) for quantitative variables. For stepwise regression analysis of clinical symptoms and signs, the most significant characteristics (duration of symptoms, age, gender, education, physical work load) and the MRI classification were selected for the evaluated outcomes (back pain, disability and SLR). Because of skewed distributions, a square root transfomation was applied to the scores of each outcome before the regression analysis.
Demographic variables, symptoms and clinical signs of the patients with sciatica were analyzed by the presence of the Trp2 allele and the significancies were tested with the chi-square or Fisher’s exact test (2x2 tables) for nominal and ordinal variables, and the Student’s t-test or Kruskal-Wallis test for quantitative variables. Three controls of similar age and occupation, and from the same gender were selected for each of the patients with the Trp2 allele. MRI findings of the patients with the Trp2 allele and their controls, and family members with and without the Trp2 allele were investigated by contingency tables and chi-square or Fisher’s exact test.
The presence of TLS was analyzed by presence of the Trp3 allele, and the statistical significance evaluated with Fisher’s exact test. Logistic regression analysis was performed to clarify the determinants of TLS; these included the Trp3 allele, gender, age, duration of symptoms, occupational load, sciatic and back pain history, smoking, body mass index and height.
Demographic variables, symptoms and clinical signs of the patients with sciatica were analyzed by presence of the Trp3 allele, and the significances were tested with the Pearson chi-square or Fisher’s exact test (2x2 tables) for nominal and ordinal variables and the Student’s t-test or Kruskal-Wallis test for quantitative variables.
In the evaluation of intervertebral disc degeneration, end-plate degeneration, dorsal transverse tears, high-intensity zone lesions, and Schmorl’s nodes by Trp3 allele presence, for each of the Trp3 allele positive patients, a control matched for age, gender and occupation was selected from the patients without the allele. Matched pair analysis was warranted because determinants such as age affect disc degeneration (Miller et al 1988). The mean age of the Trp3 allele positive patients was 42.6 years compared to 42.7 years for their matched pairs. Nineteen of the total 34 pairs were concordant for occupation. The discordant pairs differed by only one category (sedentary job vs. mixed job, or mixed job vs. physical job). For the statistical analyses, end-plates were graded as normal or degenerated. The statistical significance of the differences in the MRI findings between patients with the Trp3 allele and their matched controls was investigated by the marginal homogeneity test (extension of the McNemar test) for intervertebral disc degeneration and by the McNemar test for the other MRI findings. P-values less than 0.05 were considered significant.
Analysis of covariance was performed to compare the treatments. The adjusted change in scores for the different outcomes between adjacent follow-up assessments and baseline were calculated with 95% confidence intervals. Treatment effects were determined by reducing the adjusted scores of the saline group from those of the methylprednisolone group. Additionally, the percentage of painless patients (=responders, ≥75% decrease of leg pain from the baseline scores) for both methylprednisolone-bupivacaine and saline groups were evaluated at every follow-up assessment. Operated patients were always regarded as nonresponders. The statistical significance of difference was evaluated with Fisher’s exact test. Repeated measures analysis of variance was used for the estimation of within-groups changes over time. Between-groups treatment difference over time (efficacy) was analyzed with the AUC-method (Altman 1991). The AUC-scores were adjusted, in addition to symptomatic disc level and days of sick leave before the intervention, with the baseline value of the respective outcome (except for medical costs) and duration of symptoms. The AUC-scores of selected outcomes were calculated separately from baseline to 3 months, and from 3 months to 1 year. The AUC-scores for different outcomes were adjusted also for the baseline values of the respective outcome (except for medical costs).
In order to get a cost-effectiveness estimate for the treatments, total costs by 3 and 12 months were divided by the number of treatment responders at the respective time point. The obtained figures for the steroid and saline treatments were compared by Student’s t-test.
The efficacy and cost-effectiveness were evaluated with respect to the duration of symptoms, age, the symptomatic disc level, and the MRI classification. For MRI classification, noncontained herniations and sequesters were combined as extrusions. Age of patients did not have any significant effect on the treatment differences. Duration of symptoms modified the total costs at 6 months so that the patients with shorter symptom duration (≤ 2 months) before the intervention had greater monetary savings with the steroid injection. Therefore the AUC-scores for medical costs have been adjusted also for symptom duration. The rate of operations in different subgroups was evaluated by Kaplan-Meier curves and log-rank tests (Altman 1991). P-values less than 0.05 were considered statistically significant. For the statistical analysis, SPSS version 8.0 (SPSS Corp., Chicago, IL) was used.