A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection.

OBJECTIVE: To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS: A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed. RESULTS: The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034). CONCLUSIONS: Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings.

Dental hygiene work in a clinical trial.

UNLABELLED: Dental hygiene activities were developed as part of a randomized clinical trial designed to assess the safety of low-level mercury exposure from dental amalgam restorations. Along with dental-hygiene clinical work, a community programme was implemented after investigators noticed the poor oral hygiene habits of participants, and the need for urgent action to minimize oral health problems in the study population. OBJECTIVES: Clinical and community activity goal was to promote oral health and prevent new disease. Community activities involved participants and their fellow students and were aimed at providing education on oral health in a school environment. METHODS: Dental hygienists developed clinical work with prophylaxis, sealants application and topical fluoride and implemented the community programme with in-class sessions on oral health themes. Twice a month fluoride mouthrinses and bi-annual tooth brushing instructional activity took place. Participation at dental-hygiene activities, sealed teeth with no need of restoration and dental-plaque-index were measures used to evaluate success of the programme for the participants. RESULTS: Improvement in dental hygiene is shown by the decrease in dental plaque index scores (P < 0.0001); also sealants integrity is achieved in 86.3% of teeth. 888 (13.7%) teeth with sealants had to be restored or were lost. Children participated actively on dental hygiene activities. Teachers became aware of the problem and included oral-health in school curricula. CONCLUSION: Dental hygiene activities have shown to be helpful to promote dental hygiene, promote oral health and to provide school-age children with education on habits that will be important for their future good health.

Evaluation of a 7-year school-based community dental hygiene programme in Portugal by high school teachers.

OBJECTIVES: To obtain high school teachers evaluation of a Community Dental Hygiene programme, developed as part of a clinical trial designed to assess the safety of low-level mercury exposure from amalgam restorations. METHODS: A questionnaire to assess programme evaluation, personal opinion on programme relevance and satisfaction with activities was distributed among teachers. It had a total of 22 questions organized into three groups. RESULTS: A total of 25 questionnaires were obtained from teachers who participated in the programme. Ninety-two per cent of the respondents had a positive opinion concerning the existence of the programme. Eighty-eight per cent of the teachers believed that the programme changed student's knowledge about dental hygiene. Ninety-two per cent of teachers supported the existence of the programme and 88% of them disagreed with a statement that participation in the programme was a waste of time. Teachers who did not collaborate actively with dental hygiene activities indicated belief that the programme affected school activities (P = 0.003). Teachers who actively participated in the programme believe that dental hygiene activities were important for students (P = 0.005). CONCLUSIONS: Teacher evaluations of this kind of programme are critical for the development of school-based Dental Hygiene Education programmes. Teachers believe that Dental Hygiene Education is crucial for students' well-being.

Our Essential and Endangered Dentist-Scientist Workforce.

Future advances in dental medicine rely on a robust and stable pipeline of dentist-scientists who are dedicated to research inspired by the patients' condition. The biomedical research community faces external and internal pressures that have been building over years. This is now threatening the current and future status of basic, translational and patient-oriented research by dentist-scientists who study dental, oral and craniofacial diseases, population sciences, and prevention. The dental academic, research and practicing communities can no longer ignore the warning signs of a system that is under considerable stress. Here, the authors report findings of the Physician-Scientist Workforce Working Group, charged by the National Institutes of Health (NIH) Director, to perform quantitative and qualitative analyses on dentist-scientists by addressing the size, composition and activities of the group, relative to other health professions. From 1999 to 2012, trends in the numbers of grant applications and awards to dentist-scientists point to an overall decline. Disturbing are the low numbers of new investigators who apply for Early Career NIH Programs. While more seasoned dentist researchers enjoy greater success, the average age of first-time funded dentists is 52.7 y for females and 54.6 y for males, with a relatively low number of applications submitted and funded. These new data led the panel to stress the need to expand the capacity of the dentist-scientist workforce to leverage technologies and research opportunities that benefit the profession at-large. Suggestions were made to invest in developing clinical research faculty, including those with foreign degrees, through new training mechanisms. The creation of new alliances between national organizations like the American Association for Dental Research, the American Dental Education Association and the American Dental Association will undoubtedly lead to bold and concerted actions that must be pursued with a sense of urgency. A more supportive culture within dental schools and universities for dentist-scientists is needed, as their success is critical to the future career choices of their mentees. Knowledge Transfer Statement: Advances in dental medicine rely on a pipeline of dentist-scientists who are dedicated to research inspired by the patients' condition. Despite the recent advancement in technology and innovation, the dental community can no longer ignore the various pressures that threaten the future of the dentist-scientist profession. Here, the authors report findings of the Physician-Scientist Workforce Working Group of NIH that were published in 2014, and draw attention to the key issues threatening the NIH-funded pool of dentist-scientists.

Enhanced risk assessment for primary coronary heart disease events by maximal exercise testing: 10 years' experience of Seattle Heart Watch.

A 10 year prospective community practice study in Seattle of risk of primary morbidity (defined by hospital admission) and mortality due to coronary heart disease in 3,611 men and 547 women initially free of clinical manifestations of this disease revealed a crude incidence of 202 coronary heart disease events, or 4.9% in 6.1 +/- 2.6 years of follow-up. The case fatality rate was 16.8%. Stratification by clinical classification of asymptomatic healthy persons versus patients with atypical chest pain syndrome (not angina pectoris) and hypertension (as classified by physicians) showed an incidence rate of primary events due to coronary heart disease of 2.9, 5.5 (not significant) and 10.0% (p less than 0.001), respectively. Identification of conventional risk factors is known to be important for risk assessment. However, the presence of any conventional risk factor, in conjunction with two or more selected maximal exercise predictors (which vary with the clinical classification) at enrollment, substantially increased the cumulative 6 year incidence rate to 24.3, 15.5 and 33.3% in asymptomatic healthy men, patients with atypical chest pain syndrome and hypertensive patients, respectively. Observation of the exercise predictors in the absence of conventional risk factors increased the risk much less, suggesting that the use of maximal exercise testing for risk assessment in those with no clinical manifestations of disease might be limited to persons with one or more conventional risk factors.

Goiter prevalence and bacterial contamination of water supplies.

Previous epidemiological studies have shown a significant statistical correlation (P < 0.005 to P < 0.0005) between goiter prevalence and rock types in the watersheds that supply 37 localities in Western Columbia. Bacterial contamination has also been implicated as a cause of endemic goiter. We, therefore, did bacteriological studies to incorporate this variable into the statistical model in 34 of the 37 localities previously surveyed. Samples of the water in the 34 localities were taken at the water source or intake of water supply and at the pipeline system in households and schools. Samples were collected in sterile bottles and cultured on several media for 48 h. The number of bacteria per ml was determined by Quebec's camera and the bacteria (E. coli, Bacillus sp., K. pneumoniae, Proteus sp., and Neisseria sp.) were identified according to conventional methods. Multiple regression analysis and the logistic regression model were used to analyze the data. Only two variables had significant relationships with goiter prevalence: K. pneumoniae in the water source (P < 0.01) is related to a lower prevalence and the overall concentration of bacteria in the pipeline system (P < 0.05) is related to a higher prevalence. Multiple regression analysis to compare the effects of bacteriological variables to those of geological variables indicating rock types showed sedimentary rocks in the watershed associated (P < 0.005) with higher goiter prevalence and an increased concentration of K. pneumoniae in the water source again associated (P < 0.025) with lower goiter prevalence. Bacterial concentration in the pipeline system was of marginal importance (0.05 < P < 0.10). Thus, the presence of sedimentary rocks was the best indicator of disease. A second best indicator was the concentration of K. pneumoniae in the water source. We hypothesize that the lower goiter prevalence associated with K. pneumoniae may be a natural example of biodegradation of the organic contaminants that produce goiter.

Prognostic and predictive value of exertional hypotension in suspected coronary heart disease.

The prognostic and predictive value of exertional hypotension was assessed in 1,241 patients having treadmill maximal exercise testing, coronary arteriography, and follow-up averaging 5.4 years. Medically treated patients with coronary artery disease (CAD) with exertional hypotension had poorer survival than did those without such hypotension; however, maximum systolic pressure during exercise was a more powerful predictor of survival. Patients with exertional hypotension had more extensive CAD and more left ventricular (LV) dysfunction than did patients who had an increase in blood pressure with exertion; these findings probably account for the impaired survival. However, exertional hypotension, was an insensitive indicator of significant left main coronary artery stenosis, 3-vessel disease, or severe resting LV dysfunction.

Variations in and significance of systolic pressure during maximal exercise (treadmill) testing.

Variations in clinical noninvasive systolic pressure at the point of symptom-limited exercise on a treadmill were examined in six groups of subjects: 5,459 men and 749 women classified into three categories each. Among the men, 2,532 were asymptomatic healthy, 592 were hypertensive and 1,586 had clinical manifestations of coronary heart disease (that is, typical angina pectoris, prior myocardial infarction or sudden cardiac arrest with resuscitation). Among the women, 244, 158 and 347 were in the corresponding clinical categories. None had had cardiac surgery; all had follow-up status ascertained by periodic mail questionnaires. Reported deaths were reviewed and classified by three cardiologists; 140 deaths were attributed to coronary heart disease, 118 of them in the men classified as having coronary heart disease. The majority of maximal systolic blood pressure readings were reported to the nearest centimeter rather than millimeter of pressure. Retesting of 156 persons from 1 to 32 months later showed that pressure values agreed within 10 percent in two thirds, the overall mean difference was only 8.6 mm Hg and the correlation at maximal exercise was superior to that of the resting observations just before exercise. Hypertensive patients had a significantly greater body weight than normotensive persons. Among men, the lowest maximal systolic pressure was observed in the group with coronary heart disease; among women, the lowest mean pressure was found in the healthy group. Patients with coronary heart disease were slightly older, and only the women showed a significant correlation in maximal pressure with age. Only 5 percent of the variation in maximal systolic pressure in the patients with coronary heart disease was due to a shortened duration of exercise. Maximal systolic pressures correlated fairly well (r equals 0.46 to 0.68 for the various groups) with resting systolic pressure, and this relation was independent of the diagnosis of cardiovascular disease in both men and women. Relations between pressure and the number of stenotic coronary arteries and imparied ejection fraction at rest were examined in 22 men without and 182 men with coronary artery disease. Lower maximal systolic pressures were often associated with two or three vessel disease or reduced ejection fraction, or both. The prognostic value of maximal systolic pressure for subsequent death due to coronary heart disease was examined in the men with coronary heart disease. The annual rate of sudden cardiac death decreased from 97.9 per 1,000 men to 25.3 and 6.6 per 1,000 men as the range of maximal systolic pressure increased from less than 140 to 140 to 199 and to 200 mm Hg or more, respectively. Cardiomegaly, Q waves in the resting electrocardiogram and persistent postexertional S-T depression were more common in men with the lowest systolic pressure at maximal exercise.

Effect of coronary artery bypass grafting on subsequent hospitalization.

The rates of hospitalization during follow-up for a matched pair cohort of medically and surgically treated patients from the Angiography Registry of Seattle Heart Watch were compared. Medically and surgically treated patients were matched according to extent of disease, left ventricular ejection fraction, age, and 3 other survival rate-related characteristics. There was a 26% reduction in cardiovascular hospitalizations in the surgically treated patients (19%/year) compared with the medically treated patients (26%/year). This was due to a significant reduction in hospitalization rate for myocardial infarction (surgically treated patients 1.1%/year, medically treated patients 2.6%/year), and for other cardiovascular reasons (surgically treated patients 12.5%/year, medically treated patients 15.7%/year). No significant (p = 0.146) reduction occurred in hospitalization rate for chest pain not due to myocardial infarction (surgically treated patients 5.6%/year, medically treated patients 7.7%/year). When the perioperative infarctions are included for the surgical cohort, the overall myocardial infarction rate is not significantly different (p = 0.173) between the 2 treatment groups (surgically treated patients 1.9%/year, medically treated patients 2.6%/year). Acute myocardial infarction was an uncommon reason for hospitalization, accounting for only 8% (55 of 685) of all cardiovascular hospitalizations, and was not related to the number of stenotic vessels in medically treated patients.

Effect of aortocoronary saphenous vein bypass grafting on death and sudden death. Comparison of nonrandomized medically and surgically treated cohorts with comparable coronary disease and left ventricular function.

The effect of saphenous vein bypass grafting on the incidence of sudden cardiac death and total cardiovascular death was studied by comparing the survival of subsets of surgically and medically treated patients with coronary disease who were similar in two major prognostic variables: extent of coronary disease and ejection fraction. Significant differences in some baseline variables existed between medical and surgical subgroups with similar ejection fraction and extent of coronary disease. Medically treated patients tended to be in a lower functional class, to have more extensive ventricular contraction abnormalities, to have a larger end-diastolic volume, and to have fewer distal vessels feasible for grafting. Surgically treated patients with two vessel disease and normal or moderately reduced election fraction had improved survival when compared with medically treated patients with two vessel disease and similar ejection fraction. Improved survival of borderline statistical significance was also seen in surgically treated patients with three vessel disease and moderately reduced ejection fraction. When categorized according to end-diastolic volume, surgically treated patients with two vessel disease and normal or moderately increased end-diastolic volume also had improved survival over similarly defined medically treated patients. The sudden death rates for subgroups of mecically treated patients were 1.8 to 10.9 times higher than the rates in subgroups of surgically treated patients with a comparable extent of coronary disease and ejection fraction.

Effect of surgical versus medical therapy on return to work in patients with coronary artery disease.

The proportion of medically and surgically treated patients with coronary artery disease working full time 1 year after cardiac catheterization or surgery, respectively, was assessed by questionnaire in a registry of patients who had had coronary angiography. The proportion of medically and surgically treated patients working 3 months before catheterization or surgery was 74 percent (148 of 201) and 75 percent (899 of 1,198), respectively, whereas 62 percent (125 of 201) and 62 percent (747 of 1,198), respectively, were working full time 1 year after catheterization or surgery. Multivariate analysis identified five variables predictive of return to work. In order of significance these were: working status 3 months before surgery or catheterization, years of education, age, functional class before surgery or catheterization and period of not working before surgery or catheterization. Work status 3 months before surgery or catheterization was clearly the best predictor of continued employment 15 months later. Surgical therapy was not more effective than medical therapy in maintaining full-time employment in this registry of patients with coronary artery disease.

Myocardial imaging with 201thallium: an analysis of clinical usefulness based on Bayes' theorem.

Rest-exercise thallium-201 (201Tl) myocardial imaging and rest-exercise electrocardiography were performed in 137 patients with suspected coronary artery disease (CAD). The final diagnosis of coronary disease was made by arteriography. Sensitivity and specificity for the ECG and thallium studies alone or combined were then determined. Based on these data, the posttest probability of CAD with a normal or abnormal test was calculated using Bayes' theorem for disease prevalences ranging from 1%--99%. The difference between the probability of disease with a normal test and the probability of disease with an abnormal test was also calculated for each prevalence range. The results demonstrate that 201Tl imaging discriminates between disease absence or presence better than does the ECG. However, both the ECG and thallium studies provide rather poor discrimination between disease and no disease when the disease prevalence is low (less than 0.20) or high (greater than 0.70). Because of this characteristic, it is unlikely that screening tests for CAD will prove useful unless the disease prevalence in the group under study is in the moderate (0.20--0.70) range.

Determination and selection of the optimum number of sites and patients for clinical studies.

Calculating required sample sizes is a critical step in the design of any study. For dental studies, the sample size needs to be specified at two levels: (1) the number of patients (n) enrolled in the study, and (2) the average number of sites (m) examined per patient. In general, m and n should be selected in such a way that the precision of the research findings is maximized, while the cost of the study is minimized. This objective can be realized by taking stock of the components of variation and the costs involved with enrolling patients and examining sites. The research cost for n patients ($C1/patient), at an average of m sites per patient ($C2/site), can usually be approximated by nC1 + nmC2. The precision varies as a function of the variance components, m, and n. To optimize precision for a fixed cost, the average number of sites examined per patient (m(opt)) should be approximately equal to [formula: see text] where rho is the within-patient correlation coefficient of the site-specific variable measured. When m(opt) is approximately equal to or in excess of the average number of sites available per patient, whole-mouth examinations are indicated. When m(opt) is considerably smaller than the average number of sites available, the sample of optimum size should be obtained by some random mechanism. Examination of a number of sites considerably different from m(opt) results in a waste of resources, regardless of the number of patients studied. Standard statistical analyses for determination of the patient sample size required to obtain a pre-specified precision or power are discussed.

Statistical issues in periodontal research.

In the past 10 to 12 years, there have been several statistical issues identified in periodontal research which require and have generated non-standard or new statistical approaches. The purpose of this paper is to give an overview of these issues and approaches. Three general categories of issues are described: (i) statistical methods for detecting when disease progression occurs, and biological theories and corresponding statistical models which attempt to describe how the disease progresses; (ii) design issues in studies of therapeutic efficacy; and (iii) analytic issues arising from periodontal data analysis.

Pre-existing cardiovascular disease and periodontitis: a follow-up study.

Periodontal infections in individuals with pre-existing heart disease are believed to increase the risk for future coronary heart disease (CHD) events. The goal of this study was to search for an association between periodontitis and CHD events among individuals with pre-existing heart disease, reported in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Dentate adults (n = 636) with a history of pre-existing cardiovascular disease were followed for CHD events. The presence of periodontitis and gingivitis did not increase CHD risk among these at-risk individuals (hazard ratio [HR], 0.97, and 95% confidence interval [CI], 0.72-1.31; and HR, 1.09, and 95% CI, 0.79-1.50, respectively). When limited to individuals with a self-reported prior heart attack, periodontitis was associated with a 34% decreased CHD risk (HR, 0.66; 95% CI, 0.42-1.05). It is concluded that periodontitis or gingivitis does not elevate CHD risk among individuals with a prior heart attack or self-reported pre-existing cardiovascular disease.

Between-subject and within-subject statistical information in dental research.

The evaluation of risk factors in dental research frequently uses observations at multiple sites in the same patient. For this reason, statistical methods that accommodate correlated data are generally used to assess the significance of the risk factors (e.g., generalized estimating equations, generalized linear mixed models). In applications of these methods, it is typically assumed (implicitly, if not explicitly) that between-subject and within-subject comparisons will produce the same estimated effect of the risk factor. When between- and within-subject comparisons conflict, the statistical methods can give biased estimates or results that are difficult to interpret. For illustration, we present two examples from periodontal disease studies in which different statistical methods give different estimates and significance levels for a risk factor. Statistical analyses in dental research should assess whether different sources of information give similar conclusions about risk factors or treatments.

Bias induced by self-reported smoking on periodontitis-systemic disease associations.

Non-causal associations between periodontitis and systemic diseases may be spuriously induced by smoking because of its strong relationship to both. The goal of this study was to evaluate whether adjustment for self-reported smoking removes tobacco-related confounding and eliminated such spurious confounding. Using NHANES III data, we evaluated associations between attachment loss and serum cotinine after adjustment by self-reported number of cigarettes smoked. Cotinine, a metabolite of nicotine, should not be related to attachment loss, if self-reported smoking captures the effect of tobacco on attachment levels. Adjustment for self-reported cigarette smoking did not completely remove the correlation between attachment loss and serum-cotinine level (r = 0.075, n= 1507, p = 0.003). Simulation studies indicated similar results for time-to-event data. These findings demonstrate the difficulty in distinguishing the effects of periodontitis from those of smoking with respect to a smoking-related outcome. Future studies should report results of analyses on separate subcohorts of never-smokers and smokers.

Efficiency issues among statistical methods for demonstrating efficacy of caries prevention.

Although repeated tooth-surface-specific information is commonly collected during a longitudinal caries clinical trial, traditional methods often make limited use of the repeated measures. Newer methods of analysis, such as methods based on time-to-event and methods for longitudinal or clustered data, have the potential to increase the efficiency of the statistical analysis. We compare a range of analytical methods from the traditional analysis based only on the number of caries onsets to newer methods that incorporate time at risk and surface-specific information, such as Poisson regression methods for clustered data, with respect to the efficiency of treatment comparisons. Under most circumstances, the greatest gain in efficiency associated with time-to-event methods will be due to the ability of subjects to contribute caries onsets to the analysis until they are lost from the study. Incorporating the number of surfaces at risk, the surface time at risk, and surface-specific characteristics will typically produce only a modest gain in efficiency.

Evaluating the validity of probing attachment loss as a surrogate for tooth mortality in a clinical trial on the elderly.

Most periodontal trials are based on the assumption that the superior treatment, as judged by short-term intangible changes in probing attachment levels (the surrogate), is also the treatment most likely to affect tooth mortality. This assumption is valid if: (1) the surrogate is informative about tooth mortality, and (2) the surrogate captures a substantial proportion of the treatment effect on tooth mortality (e.g., > 50% or 75%). The goal of this study was to evaluate whether both conditions were satisfied in a randomized controlled trial (RCT) of elders at high risk for dental diseases. The results suggested that the first condition for a valid surrogate was satisfied: Both one- and two-year changes in probing attachment level were informative about tooth mortality risk. A 1-mm loss measured over a one-year period was associated with a 56% increased tooth mortality risk (relative risk = 1.56; 95% confidence interval, 1.08 to 2.26; p = 0.017); a 1-mm loss measured over a two-year period was associated with a 102% increased risk for tooth mortality (relative risk = 2.02; 95% confidence interval, 1.26 to 3.25; p = 0.004). The second condition necessary for a valid surrogate could not be confirmed in the present trial. With 95% confidence, it was concluded that one-year changes in probing attachment level measurements did not capture a significant proportion of the treatment effect (point estimate, 6%; 95% confidence interval;-38% to 53%). No useful statements could be made regarding the proportion of treatment effect captured by two-year changes, due to the width of the confidence interval (point estimate, 18%; 95% confidence interval;-151% to 140%). It is concluded that (1) the evidence surrounding the one-year change in probing attachment level indicates that it can be ruled out as being anything more than a weak surrogate marker for tooth mortality, and (2) further research is required to study the validity of two-year change in probing attachment level as a surrogate marker. Due to characteristics of the population and the treatments investigated, the generalizability of these findings to other RCTs is questionable.

Within-subject coronal caries distribution patterns: an evaluation of randomness with respect to the midline.

The distribution of caries among homologous surfaces can exhibit three possible patterns: random, aggregated, or regular. In a random caries pattern, caries lesions are randomly distributed among homologous surfaces. An aggregated caries pattern is distinguished by the aggregation of lesions on one side of the mouth or the other to a greater extent than would be expected by chance alone. For a regular caries pattern, the left-right distribution of lesions is more homogenous than would be expected by chance alone. A test statistic based on the left-right distribution of caries lesions among discordant homologous pairs was developed to investigate which of these three caries patterns is present in a representative sample of the adult United States population. The data originated from the National Survey of Oral Health in the US (Employed Adults), 1985-1986. Of the 15,132 subjects studied, 12,776 subjects had 2 or more decayed or filled teeth. (At least 2 carious or filled teeth are required for detection of patterns.) Approximately 50% of these subjects (n = 6,439) had two or more discordant homologous tooth pairs. With these tooth pairs, the hypothesis of a random caries pattern was rejected in favor of an aggregated caries pattern (p < 0.0001). Similar findings were obtained with discordant homologous surface pairs. This aggregation of caries on one side of the mouth or the other may be due to genetic, infectious, and/or environmental factors.