The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Outcomes and Metrics of Pharmacogenetic Implementations Across Diverse Healthcare Systems.

Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real-world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene-drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs.

Effects of perceived patient attributes on dentist communication behavior.

The current study was designed to assess the relationship between dentists' communication behavior and their perception of patient attributes such as likeability, manageability, and prognosis. Six AEGD residents were videotaped, and their verbal and nonverbal communication behavior was analyzed in the manner described. Each resident was administered a 20-item questionnaire to determine his/her perception of patient attributes. For overall dentist nonverbal behavior, perception of the patient and the amount of recognized interruptions that the dentist allowed were significantly correlated (r = 0.28, p < 0.05). When the three dentist perception subcategories--Likeability, Manageability, and Prognosis--were analyzed, verbal and nonverbal communication leads were significantly correlated with the dentists' perceptions of patient attributes in each. The hypothesis of a relationship between patient communication behavior and the dentists' perceptions of patient attributes was supported. The results suggest that dentists alter their communication behavior depending on their assessment of various patient qualities. Whether training in interviewing techniques and communication behavior would have an effect on this process is unknown and should be addressed.

Relative reactivity of lysine and other peptide-bound amino acids to oxidation by hypochlorite.

Antibacterial and inflammatory responses of neutrophils and macrophages produce hypochlorite as a major oxidant. Numerous side chains of amino acids found in extracellular proteins can be modified by hypochlorite, including His, Arg, Tyr, Lys, Trp, and Met. We studied the relative reactivity of each of these amino acid residues in short N-blocked peptides, where other residues in the peptide were highly resistant to hypochlorite attack. Hypochlorite treatment led to modified peptides in each case, which were detected by changes in retention on reversed-phase HPLC. A distinct single product, consuming two equivalents of hypochlorite per equivalent of peptide, was obtained from the Lys-containing peptides. UV spectroscopy, nuclear magnetic resonance (NMR), and electrospray/mass spectroscopy identified this product as the dichloramine at the epsilon-amino group of the Lys side chain. The dichloramine at Lys did not decompose to form a detectable amount of carbonyl reactive with dinitrophenylhydrazine. The dichloramine at Lys did however quantitatively revert back to Lys during HCl digestion of the tetrapeptide for amino acid analysis, with simultaneous modification of the adjacent Phe residue. The formation of the dichloramine at Lys was not blocked by peptides or acetylated amino acids that contained Tyr, His, or Arg. In contrast, the presence of equimolar Met-containing peptide, or N-Acetyl-Trp, both inhibited the formation of the dichloramine at Lys. Thus, Met and Trp side chains of proteins might be able to protect Lys from chloramine formation under some circumstances, but this interpretation must consider that Met and Trp are typically found in relatively inaccessible hydrophobic sites, whereas lysine is typically exposed on the protein surface. The hierarchy of amino acid reactivities examined here will aid in the prediction of residues in biological samples most likely to be modified by hypochlorite.

Dr. Basil Bibby: early fluoride investigator and intellectual provocateur.

Dr. Basil Bibby assumed many roles during his productive career as a researcher, teacher, and administrator. Although best known for his research on oral microbiology and on foodstuff as it relates to dental caries, and for fostering the careers of many distinguished researchers, he played an important generative role in determining the local cariostatic effects of fluoride. His seminal work in this area has not received its due because of the mixed success of his initial clinical studies. We hope that a review of his contributions in this area will bring those contributions into focus and illustrate his open personality and multi-dimensional approach to research.

A survey of faculty practices in U.S. dental schools.

In addition to providing a mechanism for maintenance and enhancement of the clinical skills of the faculty, intramural faculty practices are seen as an increasingly important source of revenue for dental schools. In this paper, we report on a survey conducted during academic year 1993/94 of United States dental schools as to the existence, organization, physical structure, finances and governance of their faculty practices. Results showed that all dental schools surveyed had some form of faculty practice or plan to establish a faculty practice in the future. The mean gross income of schools with established faculty practices in the 1993/94 academic year was 1.55 million dollars. Almost all sub-disciplines were represented in these faculty practices. More than 90 percent of the practices are housed within the dental school. The major cost to the faculty practice was staff salaries, with approximately 40 percent of the gross going to faculty reimbursement. Although 60 percent of the faculty practices surveyed were under the direct control of the dental school administration, a significant number of faculty practices were either corporations or partnerships. The results of the survey indicate a continuing trend towards the establishment of dental school-based intramural practices as a means of supporting the dental school budget.

Patient satisfaction in a regular and after-hours dental clinic.

To determine whether financial incentives would have an impact on the quality of care, we compared patient satisfaction in a "regular" daytime postdoctoral general dentistry clinic and an "after-hours" clinic, using a 14-item mail questionnaire to a randomly selected sample of adult patients, stratified by age and gender. The providers in both clinics were identical; however, the method of compensation was different. When residents treated patients in the regular clinic, they were paid a fixed stipend, while the "after-hours" clinic residents' compensation was fee-for-service. The percentage of patients giving very favorable or favorable responses was high in both clinics. However, the response of patients in the "after-hours" clinic was more favorable for total number of visits required for care to be completed, management of pain, and politeness of receptionists. This study demonstrated that the payment of financial incentives to residents did not reduce and may even have enhanced patient satisfaction.

Michael Buonocore and the Eastman Dental Center: a historic perspective on sealants.

Dr. Michael Buonocore is known for his innovative research on the preparation of the enamel surface with a weak acid to enhance adhesion of an organic plastic chemical sealant and the polymerization in situ of a sealant with ultraviolet light. His co-workers at Eastman Dental Center aided and extended his research findings. The purpose of his original research was the development of a sealant to prevent occlusal caries on posterior teeth. However, the major impact of his work has been the development of adhesive restorative techniques. Although it has been demonstrated that (i) bacteria tend to die out and caries does not progress if early caries lesions are inadvertently sealed, (ii) sealant retention rates are favorable, and (iii) sealants are cost-effective, the use of sealants by the profession is still far short of early expectations.

The growth of postdoctoral general dentistry programs.

From 1972 to 1990, the number of Postdoctoral General Dentistry (PGD) programs increased by 57% and enrollment increased by 57% and enrollment increased by 131% for a total of 118 PGD programs and 1,367 positions. Although there has been some increase in military and Veterans Affairs (VA) programs, the major increase was in civilian programs. From 1972-78, the major impetus for growth was hospital sponsorship of General Practice Residency (GPR) programs. With federal funding of PGD programs, civilian GPR programs continued to be the main source of growth until the accreditation of Advanced Education in General Dentistry (AEGD) programs in 1981. Subsequently, almost all increases were in AEGD programs. Over the 12-year period of federal funding (1978-90), there was an increase of 406 civilian PGD positions to make a total of 925 positions. The increase in enrollment directly attributable to federal funding was 242. The "unmet demand" for PGD programs was estimated to be approximately 300 positions for 1990, from data derived from the Survey of Dental Seniors and the Matching Program. Assuming that the number of PGD positions continues to increase by 35 positions a year, as it has in the past 12 years, the unmet demand would be met in slightly less than 10 years. If, however, a postdoctoral year was mandated for licensure, the increase in the number of positions would be far short of projected need.

Practice characteristics of graduates of postdoctoral general dentistry programs.

A mail questionnaire was sent to 900 dentists who completed a Postdoctoral General Dentistry (PGD) program in 1985 and 900 dentists who graduated from dental school in 1985 but did not participate in a PGD program. The response rate was 57 percent. Three-quarters of the PGD graduates trained in civilian programs with the remainder being equally divided between military and Veterans Administration (VA) programs. Graduates of military programs continued to be employed by the military five years after graduation in contrast to the VA where less than 2 percent of graduates were employed after five years. The percent of dentists who are specialists or are enrolled in specialty programs five years after graduation was approximately 13 percent and the rates were similar for PGD and non-PGD dentists. The patterns of care in private practice tended to be similar for both groups; however, in institutions GPR graduates provided more treatment for special care patients and patients who were economically disadvantaged. GPR graduates also were more involved in teaching and in hospital activities.

Removal of impacted third molars by oral/maxillofacial surgery and general dentistry residents.

The post-operative symptoms of patients who had undergone third molar extractions by Oral/Maxillofacial Surgery (OMS) residents were compared with those of patients whose extractions were performed by General Dentistry (GD) residents. The OMS group had more extractions per visit and were more likely to use intravenous sedation than the GD-treated group. No significant differences were found when the provider groups were compared by post-operative symptoms such as osteitis, infection, trismus, or paresthesia/dysthesia. The pain relief due to postoperative analgesics during the immediate 12-hour period was higher for patients treated by GD residents. Multiple regression analysis revealed that this difference was due to the number of teeth extracted and the complexity of the surgical procedure, independent of type of provider.

Effects of hyposalivatory medications on saliva flow rates and dental caries in adults aged 65 and older.

Institutionalized adults aged 65 or older often receive medications that have been associated with decreased saliva flow. Flow rates depressed by hyposalivatory medications are thought to increase susceptibility to dental caries. In this study, a cross-sectional comparison was made of stimulated whole saliva rates and coronal and root caries prevalence in a group of older adults, in a long-term care facility, taking hyposalivatory medications vs. a control group. No significant differences were found between the two groups in masticatory or gustatory stimulated flow rates or in mean decayed coronal or root surfaces.

Management of incipient caries in young adults. Dentists state their preference.

Survey finds general dentists in upstate New York use variety of treatment modalities to manage questionable or early caries in their young adult patients. The age of the dentist appears to be a factor in treatment selection, as is location of practice.

Oral yeasts, mucosal health, and drug use in an elderly denture-wearing population.

Drug use among the elderly may be a factor in oral mucosal pathology and the prevalence of oral yeasts. This study was designed to evaluate the relationship between oral yeast, denture-bearing mucosal health and drug use, especially drugs with known hyposalivatory side effects. There was an inverse relationship between denture-bearing mucosal health, and hyposalivatory drug use r = -0.41 P less than 0.04. Use of drugs with a hyposalivatory side effect was related to increased numbers of Candida glabrata but not Candida albicans in saliva and at denture stomatitis and denture sore sites.

The clinical predictability of internal derangements of the temporomandibular joint.

The value of clinical parameters as predictors of the arthrographic findings in patients with temporomandibular joint (TMJ) pain and dysfunction was examined in this study. We developed a series of simplified clinical prediction rules based on previous studies correlating clinical signs and symptoms with arthrographic diagnosis of the condition of the TMJ meniscus. One hundred eighty-six patients with signs and symptoms of TMJ dysfunction were clinically examined before TMJ arthrography. Arthrograms were performed on 246 joints (126 unilateral, 60 bilateral). The rules predicted 91 of the 246 joints to be normal when actually 59 were shown to be normal arthrographically. The rules slightly underpredicted those patients with positive arthrographic findings for internal derangements. Although there were some individual variations in the predictability of unilateral versus bilateral arthrograms (patients), there was very little overall difference, 58% and 60%, respectively. This study confirms previous suggestions that clinical findings alone are not consistently accurate in diagnosing the exact type of TMJ internal derangements depicted by arthrographic criteria.

Therapeutic use of sealants for incipient or early carious lesions in children and young adults.

Although the overall caries rate has declined significantly in the past decade, recent studies have shown that caries in occlusal pits and fissures continues to be a significant problem in adolescents and young adults. Radiographic and bacteriologic studies of sealed carious teeth were originally designed to allay the profession's concerns about continued progression of the carious process. These studies have demonstrated that caries is inhibited and may in fact regress under intact sealants. The changes in patterns of caries incidence and the positive results of the sealant studies suggest that alternative approaches to the treatment of incipient or early occlusal caries should be considered. In addition to the radiographic and bacteriological studies of sealed carious teeth, studies on retention over carious pits and fissures, wear, cost effectiveness and changing attitudes of dentists indicate that sealing incipient or early carious lesions is a viable alternative to restoration with amalgam.

Effects of fluoride, lithium, and strontium on growth and acid production of mutants streptococci and Actinomyces viscosus.

Eight strains of mutants streptococci and two strains of Actinomyces viscosus were studied to determine (1) their relative sensitivities to fluoride, lithium, and strontium and (2) whether lithium or strontium interact to enhance the known antimicrobial effects of fluoride. Analyses of variance of the data revealed a major inhibition of growth and acid production by fluoride, but not by lithium or strontium. Fluoride (5 mg/l) inhibited cell growth of all strains tested by a mean of 17% and total titratable acid production by a mean of 31%. However, there were marked differences between the strains. Mean total titratable acid was inhibited by fluoride least with the A. viscosus strains (15%) and most with the mutans streptococci (34%). Although interactions among the elements were statistically significant, they were generally slight in magnitude.