Neal W. Chilton

A new vehicle (orabase) for the application of drugs to the oral mucous membranes.

Abstract A new vehicle for the application of therapeutic agents to the oral mucous membranes is described. Various clinical tests were undertaken on a total of 119 patients (784 applications) in order to study the usefulness of this material as a vehicle for the prolonged application of medications to the oral mucous membranes. The findings indicate that when approximately 60 mg. (Group I), 250 mg. (Groups II and III), and 125 mg. (Group IV) of this vehicle adhesive are applied to various sites of the oral cavity, the average duration of maintenance was as follows: dorsum of the tongue—twenty-five, fifty-eight, and fifteen minutes for Groups I, II, and IV, respectively; hard palate—twenty-three, eighty-one, and thirty-three minutes for Groups I, II, and IV, respectively; anterior labial gingivae—twenty-four, 109, ninety-four, and fifty-six minutes for Groups I, II, and III, and IV; lower lingual anterior—eighty-five, sixty-four, and thirty-four minutes for Groups II, III, and IV; mucosa of the cheek—twenty-five, ninety-one, and forty-five minutes for Groups I, II, and IV; inner surface of the lower lip—103 minutes for Group II; and mucobuccal fold—152, and 108 minutes for Groups II and III, respectively. In no instance was there observed any evidence of irritation or other side reaction or toxicity, either local or systemic, due to the vehicle being studied. These data indicate a potential usefulness of this material as a vehicle for topical oral medications and mechanical protection in the oral cavity.

Design and Analytic Concepts for Periodontal Clinical Trials

Aspects of the design and analysis of periodontal clinical trials are surveyed from a biostatistical perspective. Design issues discussed include protocol preparation, subject selection and its documentation, randomization, problems associated with the sample versus population paradigm in sampling of microbes and gingival fluid constituents, quality control, cross-over and split-mouth versus parallel-arm designs, blinding, and multicenter trials. Analytic discussion deals with the definition and choice of analytic unit, appropriate methods for the analysis of data from multiple sites within the same subject, the nature and application of randomization tests, interim analyses, subgroup analyses, and multiple comparison issues. Examples are provided to illustrate the feasibility of analyzing site-specific data while accounting for intra-subject correlation, which represents the increased similarity of sites chosen from the same mouth as compared to sites from different patients. J Periodontol 1992; 63:1124-1140.

Reactions following the use of terramycin troches: A controlled study

T HERE is apparent from the literature an increasing awareness of the local and general side effects observed during topical and systemic antibacterial therapy.l-I2 Kutscher has reviewed the literature in detail concerning t,he oral reactions to antibiotic and sulfonamide therapy.l” Reports on systemic terramycin therapy indicate that its administration is accompanied by reactions of varyin g types and severity associated chiefly with the oropharyngeal region and the gastrointestinal tract.3, 14, I59 I6 However, considering the severity of the diseases under treatment and their response to systemic terramycin, the reported reactions have not usually been of sufficient importance to be considered a detriment to therapy. The topical application of terramycin in troches introduces the factor of prolonged contact of the drug with the oral mucosa. The side actions thus encountered should be weighed against the severity of t,he oral infection which requires specific treatment with topical terramycin. This study was undertaken to : (1) study and evaluate the reactions resulting from oral terramycin troche therapy; (2) attempt treatment of the reactions resulting from terramycin troche medication, the therapy to be based upon the possible causes of the reactions’” ; (3) inquire into the possibility of chemotherapeutic prophylaxis against such reactions ; and (4) determine the occurrence of systemic sensitization from topical terramycin medication.

Confidence Intervals for Percentage Reduction in Caries Increments

Confidence intervals are presented for the percentage reduction in mean caries increments associated with a test treatment relative to the mean increment associated with control. Approaches based on both the analysis of variance and the analysis of covariance are compared with respect to ease of computation and to the length of the confidence interval.

Studies in the Design and Analysis of Dental Experiments. IV. A Modified Analysis of Variance in a Clinical Toothbrushing Experiment

The subjects were divided into two groups of15 each by random alternation. This was done by tossing a coin to decide the disposition of each pair of subjects. If the head of the coin appeared upward, the first member of the pair was assigned to the H group, and the next member was automatically assigned to the T group. If the head of the coin did not appear on top, the first member was assigned to the T group, and the next member to the H group. The coin was tossed again for the second pair, i.e., the third and fourth individuals, etc. Those subjects in the H group brushed their teeth twice a day, using the electric brush for the upper jaw and the standard brush for the lower jaw, while those subjects in the T group used the electric brush on the lower teeth and the standard brush on the upper teeth. All subjects used the same brand of dentifrice. All subjects were examined by one examiner at the start of the study before the different brushes were distributed (at 0 time) and then at weekly intervals for 8 weeks (at times 1 through 8). The examiner did not know which subjects were in the H or T group or, in fact, what schedule of brushing was being followed in these groups, nor did he have access to the records of the previous examinations. Evaluations were made in terms of the P-M-A Index of Gingivitis and a Cleanliness Index.§

Studies in the Design and Analysis of Dental Experiments 12. Comparison of Two Measurements of Root Divergence

In odontometric studies, root divergence can be expressed in terms of the ratio of the projected root length to the actual root length (cosine) or as the actual angle itself. Since the distribution of the cosines is skewed and the distribution of the angles is rather symmetrical, the angle measurement is preferable. Various types of significance tests with either measurement will generally not differ greatly, because of the insensitive (robust) nature of these tests.

Studies in the Design and Analysis of Dental Experiments: 13. Balanced Incomplete Block Design

Occasionally, in clinical trials, there are more treatments to be tested than there are plots available in a block. For example, three medications may be tested in two eyes or in two jaws (plots) of the same individuals (blocks), five treatments in four jaw quadrants, four treatments in three matched groups of patients. In the usual crossover design, the individual is used on separate occasions for two or more treatments (assuming that there is no residual effect of any treatment on the outcome of subsequent treatments). Where more than two treatments are to be studied, it is desirable that each subject be given all of the treatments, if possible. If this is not practical, the treatment assignments to the individuals (plots) can be made in such a way that all treatments appear equally often, thus simplifying the analysis. The purpose of this paper is to present a study in which three dose levels of oral lozenges were under investigation and in which each individual was available for study on only two occasions.

The Latin Square Design in Clinical Experimentation

A S EXPERIMENTATION has progressed in dental research over the years, 2 more and more emphasis has been placed upon the refinement of technical procedures. By the same token, the design of experiments should be improved so as to make them more efficient to enable the investigator to draw sounder conclusions. It is the purpose of this paper to present and explain the clinical application of one such experimental design, the Latin square. This design was introduced by Fisher1 in order to control 2 factors while studying the effect of a third factor, such as treatment. An opportunity to use this type of design occurred in an experiment in which the effects of 4 drugs advocated for relaxing cerebral palsy children for operative dentistry were to be assessed.2 The drugs (treatments) were: Aplacebo, B-methylparafynol (Dormison), C-mephenesin (Tolserol), D-pentobarbital sodium (Nembutal), and E-meperidine hydrochloride (Demerol), all administered according to the standard dose per kilogram of body weight used in the institution in which the study was conducted. The drugs were dispensed by a nurse at a given time before operative dentistry was to begin, so that the dental operators did not know what medication was given. The vehicles of all the 5 treatments were similar so that the subjects would not be conditioned in their reactions by the physical nature of the medications employed. In order to control the expected individual variation in cooperativeness, each patient was given one of the drugs for the different operative occasions. In this study, 2 dentists were employed, one operating and one assisting. The operative procedures were fairly standardized. After the operative session, each dentist would score the patients cooperativeness without the knowledge of the other dentist and also without the knowledge of how the patient was scored on preceding occasions. The scores went from 1 to 4, with 1 designating the greatest cooperativeness and 4 the least. An attempt had previously been made to adjust the scoring scale so that the intervals between the scores referred to equal changes in cooperativeness. At the conclusion of the study, a very close approximation of the scores was noted for the 2 dentists. In all cases, however, the score of the operator was used. In order to balance the effects of the time of day during which the work was performed, the various appointments of each patient were scheduled at different times of the day. This factor was not controlled, however, and therefore this effect cannot be analyzed. In addition, the roles of operator and

The clinical dental trial. I. A new caries-inhibitory agent.

V ARIOUS methods of analyzing the clinical effectiveness of caries-inhibitory agents were presented in an earlier published paper.1 Since then, a conference dealing, in part, with the same general theme was held and a report of the discussions published.2 Of particular interest is the part written under the leadership of A. L. Russell, who also summarized the over-all report.3 Other papers dealing with broader aspects of the subject of clinical trials have been published.4 5 6 In addition, a relatively large number of papers have appeared which purport to show the effectiveness of new cariesinhibitory agents, particularly of dentifrices. Believing that these studies are a manifestation of the increasing interest in the clinical dental trial, the authors would like, in this present paper, to discuss, in greater detail, concepts of the design and analysis of studies dealing with caries-inhibitory agents, particularly with dentifrices.

The clinical dental trial. II. Evaluation of a relaxing drug for operative dentistry.

T HE evaluation of the effects of tranquilizing drugs is subject to tremendous variation both in the effect on the patient and in the observation of the clinician. As a result, some observers feel that the effectiveness of ataractic drugs is either extremely limited or nonexistent, while others believe they are the answer to the problems of the management of the apprehensive patient. It is the purpose of this paper to describe a study of the clinical effectiveness of a new drug in making patients more relaxed for operative dentistry. Particular emphasis will be placed upon the design of the experiment.