COMT Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial.

Propranolol is a nonselective ß-adrenergic receptor antagonist that is efficacious in reducing facial pain. There is evidence that its analgesic efficacy might be modified by variants of the catechol-O-methyltransferase (COMT) gene. We tested the hypothesis in a subset of 143 non-Hispanic Whites from a randomized controlled trial of patients with painful temporomandibular disorder (TMD). Patients were genotyped for rs4680, a single nucleotide polymorphism of COMT, and randomly allocated to either propranolol 60 mg twice daily or placebo. During the 9-wk follow-up period, patients recorded daily ratings of facial pain intensity and duration; the product was computed as an index of facial pain. Postbaseline change in the index at week 9 (the primary endpoint) was analyzed as a continuous variable and dichotomized at thresholds of ≥30% and ≥50% reduction. Mixed models for repeated measures tested for the genotype × treatment group interaction and estimated means, odds ratios (ORs), and 95% confidence limits (95% CLs) of efficacy within COMT genotypes assuming an additive genetic model. In secondary analysis, the cumulative response curves were plotted for dichotomized reductions ranging from ≥20% to ≥70%, and genotype differences in area under the curve percentages (%AUC) were calculated to signify efficacy. Mean index reduction did not differ significantly (P = 0.277) according to genotype, whereas the dichotomized ≥30% reduction revealed greater efficacy among G:G homozygotes (OR = 10.9, 95%CL = 2.4, 50.7) than among A:A homozygotes (OR = 0.8, 95%CL = 0.2, 3.2) with statistically significant interaction (P = 0.035). Cumulative response curves confirmed greater (P = 0.003) efficacy for G:G homozygotes (%AUC difference = 43.7, 95%CL = 15.4, 72.1) than for A:A homozygotes (%AUC difference = 6.5, 95%CL = -30.2, 43.2). The observed antagonistic effect of the A allele on propranolol's efficacy was opposite the synergistic effect hypothesized a priori. This unexpected result highlights the need for better knowledge of COMT's role in pain pathogenesis if the gene is to be used for precision-medicine treatment of TMD (ClinicalTrials.gov NCT02437383).

Age-dependent interaction between atopy and eosinophils in asthma cases: results from NHANES 2005-2006.

BACKGROUND: Atopy is an established risk factor for asthma, and an elevated eosinophil level is a hallmark of atopic and non-atopic asthma. Whether atopy and eosinophils act independently or interact to influence asthma has clinical and public health implications. OBJECTIVE: To investigate the relationship between atopy and eosinophils in asthma. METHODS: Data on current asthma, atopy (IgE positive to ≥ 1 allergen), and blood eosinophil percent (dichotomized at the median) were obtained for persons aged ≥ 6 years from the National Health and Nutrition Examination Survey 2005-2006. Interaction on an additive scale was evaluated by estimating the prevalences of asthma for combinations of atopy (yes or no) and eosinophil percent (high or low) and calculating the excess prevalence due to interaction. RESULTS: For all ages combined, the adjusted prevalences of asthma were 4.6%, 7.6%, 6.9% and 17.2% for persons with neither factor, atopy alone, a high eosinophil percent alone and both factors respectively. The excess prevalence of asthma due to interaction was 7.2%, indicating synergism. The excess prevalence was greatest in children aged 6-17 years (15.3%), and it decreased with each older age category until it was absent in adults aged ≥ 55 years (-0.2%). In children, 94% of asthma cases attributable to the 2 factors were attributable to the interaction, whereas in the oldest adults, no cases were attributable to the interaction. CONCLUSIONS AND CLINICAL RELEVANCE: Interaction between atopy and an elevated eosinophil level in asthma cases was very strong in children but absent in the oldest adults, which suggests different mechanistic pathways for these factors by age and supports the notion that asthma is a heterogeneous disease. In addition, the age-dependent interaction between the factors has potential implications for the selection of asthma patients for treatments that would target either IgE or a high eosinophil level.

Environmental tobacco smoke and periodontal disease in the United States.

OBJECTIVES: Cigarette smoking is a leading risk factor for periodontal disease. This cross-sectional study investigated the relation between environmental tobacco smoke (ETS) and periodontal disease in the United States. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey (1988-1994). The outcome was periodontal disease, defined as 1 or more periodontal sites with attachment loss of 3 mm or greater and a pocket depth of 4 mm or greater at the same site. Exposure to ETS at home and work was self-reported. The study analyzed 6611 persons 18 years and older who had never smoked cigarettes or used other forms of tobacco. RESULTS: Exposure to ETS at home only, work only, and both was reported by 18.0%, 10.7%, and 3.8% of the study population, respectively. The adjusted odds of having periodontal disease were 1.6 (95% confidence interval = 1.1, 2.2) times greater for persons exposed to ETS than for persons not exposed. CONCLUSIONS: Among persons in the United States who had never used tobacco, those exposed to ETS were more likely to have periodontal disease than were those not exposed to ETS.

Association between extent of periodontal attachment loss and self-reported history of heart attack: an analysis of NHANES III data.

Coronary heart disease is responsible for one of every five deaths in the United States. Recent epidemiological studies have shown an association between periodontal disease and coronary heart disease. The purpose of this cross-sectional study was to verify this association using data from the third National Health and Nutrition Examination Survey (NHANES III). Data for 5564 people 40 years of age and older who had complete periodontal assessments and information on heart attack were evaluated. The outcome was the self-reported history of heart attack (yes vs. no). The main independent variable was the percent of periodontal sites per person with attachment loss of 3 mm or greater (categorized as 0%, > 0-33%, > 33-67%, and > 67%). Periodontal attachment loss was measured at two sites per tooth in randomly assigned half-mouths, one upper and one lower quadrant. The covariables included sociodemographic variables and established risk factors for cardiovascular disease. Relative to the 0% category, the unadjusted odds of heart attack increased with each higher category of attachment loss-2.2 (95% confidence interval = 1.3-3.8), 5.5 (3.4-9.1), and 9.8 (4.5-21.0), respectively. Adjustment for age, sex, race, poverty, smoking, diabetes, high blood pressure, body mass index, and serum cholesterol decreased these odds to 1.4 (0.8-2.5), 2.3 (1.2-4.4), and 3.8 (1.5-9.7), respectively. This study supports findings from previous studies of an association between periodontal disease and coronary heart disease.

Factors contributing to the poorer survival of black Americans diagnosed with oral cancer (United States).

OBJECTIVE: The purpose of this study was to identify factors that contribute to the poorer survival of blacks in the United States diagnosed with oral cancer. METHODS: Data for 6,338 whites and 1,165 blacks diagnosed from 1988 to 1993 with squamous cell carcinoma of the oral cavity and pharynx were obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program 1973-1993 Public-Use Database. The covariables were sex, age, geographic area, marital status, socioeconomic status (five census-tract measures), stage, anatomic site, grade, lymph node involvement, tumor size, and treatment. Hazard ratios were estimated with Cox regression. RESULTS: Adjusted for age and geographic area, the hazard of death from oral cancer was 1.7 (95% confidence interval: 1.5-1.9) times greater among blacks than whites. The addition of the socioeconomic status (SES) variables to the model reduced the hazard ratio for race to 1.3 (1.0-1.7). Further adjustment by stage and treatment reduced the hazard ratio for race to 1.1 (0.9-1.4). In a model containing all covariables (except lymph node involvement and tumor size), the hazard ratio for race remained 1.1 (0.9-1.4). Analyses with the outcome death from any cause gave similar results. CONCLUSIONS: Lower SES, more advanced stage, and differences in treatment accounted for 86% of the excess hazard of death from oral cancer among blacks.

Racial differences in stage at diagnosis of screenable oral cancers in North Carolina.

OBJECTIVE: This study examined differences between blacks and whites in stage at diagnosis of screenable oral cancers. METHODS: Data for 1,137 North Carolina residents with first primary tumors of the oral cavity (excluding the lip and salivary glands) or oropharynx diagnosed from 1990-92 were obtained from the North Carolina Central Cancer Registry. The outcome variable was stage at diagnosis dichotomized as localized and advanced. The explanatory variables were race, sex, age, year diagnosed, tumor site, and county-level socioeconomic and health care resource factors. Bivariate, stratified, and multiple regression analyses were conducted. RESULTS: In the regression analysis, the odds of advanced stage was 2.1 (95% CI = 1.5, 2.9) times greater for blacks than whites. Other multivariable effects were sex [males compared to females: OR = 1.5 (95% CI = 1.2, 2.0)] and tumor site (oropharynx compared to palate: OR = 4.2 (95% CI = 2.5, 7.0)]. CONCLUSION: Among black and white residents of North Carolina diagnosed with cancer of the oral cavity or oropharynx, blacks had a greater odds of diagnosis at advanced stage.

The determination of underivatized chlorophenols in human urine by combined high performance liquid chromatography mass spectrometry and selected ion monitoring.

A method for the determination of underivatized chlorophenols in human urine samples by combined high performance liquid chromatography mass spectrometry is described. Results obtained on individual samples are reported and compared with data obtained by alternative chromatographic methods.