Analyzing essays about treating adults with special health care needs and intellectual and developmental disabilities.

OBJECTIVE: Analyze reflection essays written by one graduating class of students after an initial experience in a clinic for adults with special health care needs (SHCN) and intellectual and developmental disabilities, to draw insights from the patterns of observations expressed. METHODS: Essays were written by students from the University of Colorado School of Dental Medicine during the 2016-2017 academic year after completing a 1-day clinical experience treating this patient population. Readers identified 18 primary themes (PTs) previously identified in essays written during 2012-2013. RESULTS: The PT Complex communicating through third party was identified in 79.4% of essays. Least common were Frustrated patient could not understand (1.9%) and Frustrated patient could not talk (1.9%). Nine PTs were grouped to represent 3 component themes (CTs): CT1 Communication challenges, CT2 Behavioral challenge, and CT3 Altruistic responses. This grouping showed moderate internal reliability. A fourth, CT4 Emotional challenges, was rejected due to low internal reliability. CT1 was most frequently identified, followed by CT3 then CT2. Three PTs were chosen as indicative of desirable outcomes and were labeled outcome themes (OTs): OT1 Willing to see patients with SHCNs after graduation, OT2 Would like more Special Care Clinic (SCC) experiences in the future, and OT3 Looking forward to next SCC experience. Associations between CTs and OTs were not statistically significant, but provided useful insights. CONCLUSION: Reflection essays indicate discussion of strategies to manage behavioral challenges and encouragement of altruistic feelings are both vital in orientation sessions. These topics may be critical to positive student perceptions of the experience.

Effect of sugammadex on QT/QTc interval prolongation when combined with QTc-prolonging sevoflurane or propofol anaesthesia.

BACKGROUND: We evaluated the potential for QT/corrected QT (QTc) interval prolongation after sugammadex given with propofol or sevoflurane anaesthesia. METHODS: This was a two-factorial, randomized, parallel-group study in 132 healthy subjects. Anaesthesia was maintained with sevoflurane or propofol. At ~20 min following sevoflurane/propofol initiation, sugammadex 4 mg/kg or placebo was administered. Neuromuscular blocking agents were not administered. Electrocardiograms were recorded regularly. The primary variable was the time-matched mean difference in the Fridericia-corrected QT interval (QTcF) change from baseline for sugammadex versus placebo when combined with propofol or sevoflurane. No relevant QTcF prolongation was concluded if the upper one-sided 95 % confidence interval (CI) was below the 10 ms margin of regulatory non-inferiority, up to 30 min post-study drug. Blood samples were taken for pharmacokinetic analysis. An exploratory analysis evaluated potential QT/QTc effects of neostigmine 50 µg/kg/glycopyrrolate 10 µg/kg in combination with propofol. RESULTS: The estimated mean QTcF differences between sugammadex and placebo ranged from -2.4 to 0.6 ms when combined with either anaesthetic. The largest upper one-sided 95 % CI for the mean QTcF difference between sugammadex and placebo was 2 ms, occurring 2 min post-dosing. Propofol and sevoflurane resulted in mean QTcF increases exceeding 10 and 30 ms, respectively. On top of these prolongations, the effect of sugammadex was negligible at all timepoints. The mean peak sugammadex concentration was 66.5 µg/mL, with exposure similar in the sevoflurane/propofol groups. The mean QTcF changes from baseline following neostigmine/glycopyrrolate in 10 healthy subjects ranged between -1.4 and 3.6 ms. CONCLUSION: Sugammadex 4 mg/kg does not cause clinically relevant QTc interval prolongation versus placebo when combined with propofol or sevoflurane.

Half-life prolongation of therapeutic proteins by conjugation to ATIII-binding pentasaccharides: a first-in-human study of CarboCarrier® insulin.

AIM: Conjugation to antithrombin III ATIII-binding pentasaccharides has been proposed as a novel method to extend the half-life of therapeutic proteins. We aim to validate this technological concept in man by performing a first-in-human study using CarboCarrier® insulin (SCH 900948) as an example. A rising single dose phase 1 study was performed assessing safety, tolerability, pharmacokinetics and relative bioactivity of CarboCarrier® insulin. Safety, tolerability and pharmacokinetics (PK) of single doses of CarboCarrier® insulin in healthy volunteers were explored, and the dose-response relationship and relative bioactivity of CarboCarrier® insulin in subjects with type 2 diabetes were investigated. METHODS: After an overnight fast, subjects were randomized to a treatment sequence. PK and pharmacodynamic (glucose, insulin and C-peptide) samples were obtained for up to 72 h post-dose. Effects of CarboCarrier® insulin were compared with those of NPH-insulin. RESULTS: CarboCarrier® insulin was safe and well-tolerated and no consistent pattern of adverse events occurred. CarboCarrier® insulin exposure (Cmax and AUC) increased proportionally with dose. The mean terminal elimination half-life ranged between 3.11 and 5.28 h. All CarboCarrier® insulin dose groups showed decreases in the mean change from baseline of plasma glucose concentrations compared with the placebo group. CONCLUSIONS: CarboCarrier® insulin is pharmacologically active showing features of insulin action in man. The elimination half-life of the molecule was clearly extended compared with endogenous insulin, indicating that conjugation to ATIII-binding pentasaccharides is a viable approach to extend the half-life of therapeutic proteins in humans. This is an important step towards validation of the CarboCarrier® technology by making use of CarboCarrier® insulin as an example.

Expanded function allied dental personnel and dental practice productivity and efficiency.

This study examined the impact of expanded function allied dental personnel on the productivity and efficiency of general dental practices. Detailed practice financial and clinical data were obtained from a convenience sample of 154 general dental practices in Colorado. In this state, expanded function dental assistants can provide a wide range of reversible dental services/procedures, and dental hygienists can give local anesthesia. The survey identified practices that currently use expanded function allied dental personnel and the specific services/procedures delegated. Practice productivity was measured using patient visits, gross billings, and net income. Practice efficiency was assessed using a multivariate linear program, Data Envelopment Analysis. Sixty-four percent of the practices were found to use expanded function allied dental personnel, and on average they delegated 31.4 percent of delegatable services/procedures. Practices that used expanded function allied dental personnel treated more patients and had higher gross billings and net incomes than those practices that did not; the more services they delegated, the higher was the practice's productivity and efficiency. The effective use of expanded function allied dental personnel has the potential to substantially expand the capacity of general dental practices to treat more patients and to generate higher incomes for dental practices.

Mechanism of action of a nanomolar potent, allosteric antagonist of the thyroid-stimulating hormone receptor.

BACKGROUND AND PURPOSE: Graves' disease (GD) is an autoimmune disease in which the thyroid is overactive, producing excessive amounts of thyroid hormones, caused by thyroid-stimulating hormone (TSH) receptor-stimulating immunoglobulins (TSIs). Many GD patients also suffer from thyroid eye disease (Graves' ophthalmopathy or GO), as TSIs also activate TSH receptors in orbital tissue. We recently developed low molecular weight (LMW) TSH receptor antagonists as a novel therapeutic strategy for the treatment of GD and GO. Here, we determined the molecular pharmacology of a prototypic, nanomolar potent LMW TSH receptor antagonist, Org 274179-0. EXPERIMENTAL APPROACH: Using CHO cells heterogeneously expressing human TSH receptors and rat FRTL-5 cells endogenously expressing rat TSH receptors, we determined the potency and efficacy of Org 274179-0 at antagonizing TSH- and TSI-induced TSH receptor signalling and its cross-reactivity at related follicle-stimulating hormone and luteinizing hormone receptors. We analysed the allosteric mode of interaction of Org 274179-0 and determined whether it is an inverse agonist at five naturally occurring, constitutively active TSH receptor mutants. KEY RESULTS: Nanomolar concentrations of Org 274179-0 completely inhibited TSH (and TSI)-mediated TSH receptor activation with little effect on the potency of TSH, in accordance with an allosteric mechanism of action. Conversely, increasing levels of TSH receptor stimulation only marginally reduced the antagonist potency of Org 274179-0. Org 274179-0 fully blocked the increased basal activity of all the constitutively active TSH receptor mutants tested with nanomolar potencies. CONCLUSIONS AND IMPLICATIONS: Nanomolar potent TSH receptor antagonists like Org 274179-0 have therapeutic potential for the treatment of GD and GO.

Impact of the University of Colorado's Advanced Clinical Training and Service (ACTS) Program on dental students' clinical experience and cognitive skills, 1994-2006.

The University of Colorado Denver School of Dental Medicine has operated a community-based dental education program for all of its students since 1985. A database of student productivity has been maintained in a standardized format, capable of multiyear compilation, since 1994. This study utilizes twelve years of these data to profile the type and amount of clinical treatment that can be provided by a typical fourth-year dental student during a 100-day community-based training experience. Between 1994 and 2006, the school's 423 graduates provided a mean of 922 treatment procedures per student at a mean of 498 patient visits per student. During a typical four-week clinical affiliation, each student provided a mean of approximately twenty-seven restorations on permanent teeth, sixteen restorations on primary teeth, and twenty-four oral surgery procedures (extractions). Students also gained considerable experience in periodontics, fixed and removable prosthodontics, and endodontics. Self-assessed competency ratings tended to increase after completing the program, as did willingness to treat underserved populations after graduation. About 16 percent of graduates reported planning to practice in the public sector after completing dental school. A community-based experience such as this appears to offer an opportunity to substantially augment dental students' clinical training experiences.

Colorado dental practitioners' attitudes and practices regarding tobacco-use prevention activities for 8- through 12-year-old patients.

BACKGROUND: Tobacco use is a leading risk factor for oral morbidities and mortalities such as oral cancers and periodontitis. This study characterizes the factors related to dentists and hygienists conducting tobacco-use prevention counseling with 8- through 12-year-old patients. METHODS: The study used a mailed survey of dentists (n = 434), orthodontists (n = 91) and hygienists (n = 160) practicing in Colorado to collect data on the practitioners' tobacco-use prevention counseling activity, demographic characteristics, barriers to counseling and attitudes toward tobacco use. The authors used multiple logistic regression to determine which variables were associated independently with a dental practitioner's counseling children. RESULTS: The response rate was 25.6 percent. Prevalence of tobacco-use prevention counseling for children was low (38 percent for dentists and 44 percent for hygienists). Among dentists, the perception of tobacco use in children as a problem, perceived effectiveness of counseling and perceived role of a dental practitioner in counseling children were associated positively with counseling. Lack of skills was associated negatively with counseling. Among hygienists, perceived role in counseling children was associated positively and lack of time was associated negatively with counseling. CONCLUSIONS: Few dental practitioners counsel 8- through 12-year-old patients about tobacco use. Factors related to counseling appear to be amenable to education of dentists, in particular, regarding the importance of the problem, the effectiveness of counseling and skill development. CLINICAL IMPLICATIONS: Preventing tobacco use among children is integral to promoting patients' oral health. Training dentists through continuing education should increase the frequency of tobacco-use prevention counseling with children by both dentists and hygienists.

Medicaid expenditures for orthodontic services.

INTRODUCTION: A survey was conducted in 2006 to determine, on a state-by-state basis, the availability of Medicaid-funded orthodontic treatment and, when available, the criteria and the funding rates. METHODS: All 50 states were contacted by e-mail, telephone, or standard mail to obtain answers to the following questions. Does your state provide Medicaid coverage for orthodontic services? What qualifications are required to be reimbursed? What is the patient cutoff age for reimbursement of services? Is an index used to assess malocclusion? If so, which index? What is the primary training of the reviewer? How are services reimbursed? Is limited treatment covered? Is interceptive treatment covered? What is the total amount reimbursed for 24 months of treatment for comprehensive adolescent care? RESULTS: Wide variations of responses were received from the states, with no statistical significance between any questions based on geographic regions or reimbursement rates, although some trends appeared to exist. CONCLUSIONS: This study provides state-by-state details of Medicaid programs for orthodontic services and details the extensive variations in programs.

Dose-dependent effects of UVB-induced skin carcinogenesis in hairless p53 knockout mice.

Exposure to (solar) UVB radiation gives rise to mutations in the p53 tumor suppressor gene that appear to contribute to the earliest steps in the molecular cascade towards human and murine skin cancer. To examine in more detail the role of p53, we studied UVB-induced carcinogenesis in hairless p53 knock-out mice. The early onset of lymphomas as well as early wasting of mice interfered with the development of skin tumors in p53 null-mice. The induction of skin tumors in the hairless p53+/- mice was accomplished by daily exposure to two different UV-doses of approximately 450 J/m2 and 900 J/m2 from F40 lamps corresponding to a fraction of about 0.4 and 0.8 of the minimal edemal dose. Marked differences in skin carcinogenesis were observed between the p53+/- mice and their wild type littermates. Firstly, at 900 J/m2, tumors developed significantly faster in the heterozygotes than in wild types, whereas at 450 J/m2 there was hardly any difference, suggesting that only at higher damage levels loss of one functional p53 allele is important. Secondly, a large portion (25%) of skin tumors in the heterozygotes were of a more malignant, poorly differentiated variety of squamous cell carcinomas, i.e. spindle cell carcinomas, a tumor type that was rarely observed in daily UV exposed wild type hairless mice. Thirdly, the p53 mutation spectrum in skin tumors in heterozygotes is quite different from that in wild types. Together these results support the notion that a point mutation in the p53 gene impacts skin carcinogenesis quite differently than allelic loss: the former is generally selected for in early stages of skin tumors in wild type mice, whereas the latter enhances tumor development only at high exposure levels (where apoptosis becomes more prevalent) and appears to increase progression (to a higher grade of malignancy) of skin tumors.