In this paper, we propose an alternative covariance estimator to the robust covariance estimator of generalized estimating equations (GEE). Hypothesis tests using the robust covariance estimator can have inflated size when the number of independent clusters is small. Resampling methods, such as the jackknife and bootstrap, have been suggested for covariance estimation when the number of clusters is small. A drawback of the resampling methods when the response is binary is that the methods can break down when the number of subjects is small due to zero or near-zero cell counts caused by resampling. We propose a bias-corrected covariance estimator that avoids this problem. In a small simulation study, we compare the bias-corrected covariance estimator to the robust and jackknife covariance estimators for binary responses for situations involving 10-40 subjects with equal and unequal cluster sizes of 16-64 observations. The bias-corrected covariance estimator gave tests with sizes close to the nominal level even when the number of subjects was 10 and cluster sizes were unequal, whereas the robust and jackknife covariance estimators gave tests with sizes that could be 2-3 times the nominal level. The methods are illustrated using data from a randomized clinical trial on treatment for bone loss in subjects with periodontal disease.

Although cognitive-behavioral therapies (CBT) have been demonstrated to be effective for a variety of chronic pain problems, patients vary in their response and little is known about patient characteristics that predict or moderate treatment effects. Furthermore, although cognitive-behavioral theory posits that changes in patient beliefs and coping mediate the effects of CBT on patient outcomes, little research has systematically tested this. Therefore, we examined mediators, moderators, and predictors of treatment effects in a randomized controlled trial of CBT for chronic temporomandibular disorder (TMD) pain. Pre- to post-treatment changes in pain beliefs (control over pain, disability, and pain signals harm), catastrophizing, and self-efficacy for managing pain mediated the effects of CBT on pain, activity interference, and jaw use limitations at one year. In individual mediator analyses, change in perceived pain control was the mediator that explained the greatest proportion of the total treatment effect on each outcome. Analyzing the mediators as a group, self-efficacy had unique mediating effects beyond those of control and the other mediators. Patients who reported more pain sites, depressive symptoms, non-specific physical problems, rumination, catastrophizing, and stress before treatment had higher activity interference at one year. The effects of CBT generally did not vary according to patient baseline characteristics, suggesting that all patients potentially may be helped by this therapy. The results provide further support for cognitive-behavioral models of chronic pain and point to the potential benefits of interventions to modify specific pain-related beliefs in CBT and in other health care encounters.

The objective of this study was to assess changes in levels of clinical temporomandibular (TMD) pain in relation to phases of the menstrual cycle. TMD cases were 35 women not using oral contraceptives (OCs); 35 women using OCs; and 21 men. Controls were 35 normally cycling women without TMD or other chronic pains. Subjects kept daily diaries over three menstrual cycles, reporting average and worst pain, general and premenstrual symptoms. Data were subject-centered and de-trended using the residuals from a random-effects linear regression model. To test for cyclic variation, cycles were standardized to 28 days and data were grouped into 9 periods/cycle (Days 1-3, 4-6, em leader, 22-24, 25-28). Overall levels of average pain, worst pain and symptoms did not differ across TMD subject groups. For worst pain, multivariate analysis of variance revealed a statistically significant difference across 3-day periods for normally cycling women with TMD (P=0.011) and for women using OCs (P=0.017). In both groups, TMD pain levels rose toward the end of the cycle and peaked during menstruation. In women not using OCs, there was a secondary pain peak at Days 13-15, around the time of ovulation. This peak was not seen in women using OCs. There was no statistically significant difference over time periods for men (P=0.94). Similar patterns were found for average pain, as well as PMS symptoms and general somatic symptoms. These results suggest that TMD pain in women is highest at times of lowest estrogen, but rapid estrogen change may also be associated with increased pain.

Temporomandibular disorder (TMD) pain, abdominal pain, migraine and tension-type headache are more prevalent in women than in men. This study assessed the relationship of back pain, headache, abdominal pain, TMD pain, and the presence of multiple pain conditions to gender and pubertal development in a cross-sectional, population-based survey of adolescents. We also examined the association between pubertal development and depressive and somatic symptoms, factors often associated with pain in adults. We hypothesized that prevalence of all pain conditions, as well as rates of other symptoms, would increase as puberty progresses in females, but not males. Subjects (3,101 boys and girls, 11-17 years old, selected from an HMO population) reported on the presence of each pain condition in the prior 3 months and completed scales assessing pubertal development, and depressive and somatic symptoms. Data were analyzed using descriptive statistics and multivariate logistic regression. Prevalence rates were weighted for factors affecting response. Prevalence of back pain, headache and TMD pain increased significantly (odds ratios, OR=1.4-2.0, P<0.001) and stomach pain increased marginally with increasing pubertal development in girls. Rates of somatization, depression and probability of experiencing multiple pains also increased with pubertal development in girls (P<0.0001). For boys, prevalence of back (OR=1.9, P<0.0001) and facial pain (OR=1.5, P<0.01) increased, stomach pain decreased somewhat and headache prevalence was virtually unchanged with increasing maturity. For both sexes, pubertal development was a better predictor of pain than was age. Thus it appears that pain, other somatic symptoms and depression increase systematically with pubertal development in girls.

We evaluated the short- and long-term efficacy of a brief cognitive-behavioral therapy (CBT) for chronic temporomandibular disorder (TMD) pain in a randomized controlled trial. TMD clinic patients were assigned randomly to four sessions of either CBT (n=79) or an education/attention control condition (n=79). Participants completed outcome (pain, activity interference, jaw function, and depression) and process (pain beliefs, catastrophizing, and coping) measures before randomization, and 3 (post-treatment), 6, and 12 months later. As compared with the control group, the CBT group showed significantly greater improvement across the follow-ups on each outcome, belief, and catastrophizing measure (intent-to-treat analyses). The CBT group also showed a greater increase in use of relaxation techniques to cope with pain, but not in use of other coping strategies assessed. On the primary outcome measure, activity interference, the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group (35%) than in the control group (13%) (P=0.004). In addition, more CBT than control group patients had clinically meaningful improvement in pain intensity (50% versus 29% showed > or =50% decrease, P=0.01), masticatory jaw function (P<0.001), and depression (P=0.016) at 12 months (intent-to-treat analyses). The two groups improved equivalently on a measure of TMD knowledge. A brief CBT intervention improves one-year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT.