Factors in rural community buprenorphine dispensing.

Background: There are pharmacy-related barriers to the dispensing of buprenorphine for the treatment of opioid use disorders. These include pharmacists' moral objections and mistrust of treatment regimens; the perception of a limit on the amount of buprenorphine able to be ordered and dispensed; stigma and concerns about diversion; and knowledge and communication gaps. Objectives: To document pharmacy stakeholders' awareness and interpretation of regulatory policies that may impact rural community pharmacists' willingness and ability to dispense buprenorphine. To identify factors that affect rural community pharmacists' willingness and ability to dispense buprenorphine in Appalachian North Carolina. Methods: Qualitative analysis and thematic coding of phone interviews with eight pharmacists from several rural North Carolina counties where local health departments recently began prescribing MOUD and four pharmacy industry stakeholders representing knowledge of wholesale distributors and pharmacy education. Results: Three major themes were identified: stigma and misinformation, provider-prescriber communication, and perceived and actual regulatory constraints. A number of respondents indicated a desire to better understand MOUD treatment plans and displayed a misunderstanding of evidence-based treatment guidelines. Stakeholders indicated the importance of pharmacists establishing a relationship with prescribers and described pharmacist preference for dispensing buprenorphine to established patients over new or out-of-area patients. Pharmacist stakeholders and industry/education stakeholders expressed concern over a perceived DEA 'cap' for buprenorphine ordering. Conclusions: This study provides insight on possible approaches to address rural pharmacy-related barriers patients may face when filling buprenorphine prescriptions. There is a demonstrated need for further pharmacist training on evidence-based practices for treating opioid use disorders and ordering limits, as well as a need for increased communication between prescribers and pharmacists.

Eligible Prescriber Experiences with Substance Use Disorder Treatment and Perceptions of Pharmacy Barriers to Buprenorphine.

OBJECTIVES: The primary aim of this study was to better understand North Carolina providers' specific substance use disorder (SUD) and opioid use disorder treatment practices and buprenorphine prescribing. Furthermore, this study aimed to provide novel information regarding US South and rural providers' opioid use disorder treatment behaviors and perceptions of patient experience at community pharmacies. METHODS: An online survey consisting of closed-ended and open-ended questions was used. Surveys were delivered to healthcare providers' e-mails and self-administered. Surveys were administered through an online survey platform. RESULTS: In total, 332 healthcare providers, who were eligible to be X-waivered to prescribe buprenorphine, completed the online survey. Survey participants reported not having their X-waiver to prescribe buprenorphine or actively prescribing buprenorphine. The majority of participants were uncertain of potential barriers to filling buprenorphine prescriptions. Providers treating a mix of rural and urban patients reported being less likely to screen for SUDs. Although there were no rurality differences in SUD screening, providers who treat mostly rural patients reported a lack of SUD treatment options in their area. CONCLUSIONS: Early detection of SUDs can help prevent negative health outcomes for patients. Regardless of patient rurality, providers should screen for SUDs and familiarize themselves with the patient's experience when filling a buprenorphine prescription, along with possible barriers. Furthermore, providers should incorporate questions about their patient's ability to receive buprenorphine to help ensure that patients are receiving proper and necessary treatment.

North Carolina community pharmacists' buprenorphine dispensing practices and attitudes.

BACKGROUND: Many barriers, including stocking behaviors and pharmacist attitudes, can limit access to buprenorphine in pharmacy settings. OBJECTIVES: To assess North Carolina (NC) pharmacists' (1) buprenorphine stocking behaviors, (2) awareness and interpretation of federal and state policy regarding buprenorphine, (3) perceptions about changes in buprenorphine demand, and (4) reasons for not dispensing buprenorphine, including attitudes. METHODS: A convenience sample of currently practicing community pharmacists was recruited to participate in a 10-minute online survey. The survey included demographic questions and assessed pharmacists' buprenorphine ordering, stocking, and dispensing behaviors. Descriptive statistics were calculated, and logistic regressions examined associations with whether pharmacists (1) had ever refused to fill a buprenorphine prescription and (2) perceived buprenorphine dispensing limits. RESULTS: The majority (96%) of respondents (n = 646, completion rate = 5.5%) kept buprenorphine in stock regularly or ordered it as needed, with generic formulations being stocked most often. Many pharmacists (62%) had refused to fill a buprenorphine prescription. Pharmacists with more negative buprenorphine attitudes were more likely to refuse to fill a buprenorphine prescription. Many pharmacists (31%) believed there were buprenorphine ordering limits, with wholesalers most commonly being perceived as the source. Pharmacists with more negative buprenorphine attitudes were more likely to perceive buprenorphine ordering limits, while pharmacists who worked at national chain, grocery or regional chains, and other pharmacy types were less likely to perceive ordering limits than independent pharmacies. CONCLUSION: Although most pharmacies stocked buprenorphine products, pharmacists' refusal to dispense and perceived ordering limits could limit patient access. Refusal and perceived ordering limits were associated with pharmacist attitudes and pharmacy type. Training that addresses logistical and attitudinal barriers to dispensing buprenorphine may equip pharmacists to address buprenorphine access barriers.

The effect of surface defects in early caries assessment using quantitative light-induced fluorescence (QLF) and micro-digital-photography (MDP).

OBJECTIVES: The purpose of this study was to consider the impact of surface defects on quantitative light-induced fluorescence (QLF) and micro-digital-photography (MDP) measures, in relationship to lesion depth. METHODS: Simulated enamel carious lesions were developed on 45 extracted human teeth. Images of each tooth were captured with both QLF and MDP. The teeth were sectioned and lesion depth was measured with polarized light microscopy (PLM). Pearson correlations were computed using data from the 27 lesions which did not have surface loss, and then separately based upon the 18 lesions which did display surface loss. MDP variables ΔR and ΔX measure reflected light, whereas QLF variables ΔF and ΔQ measure fluorescence. RESULTS: A strong correlation was identified between lesion depth and ΔF (r=-0.765, p<0.0001), and ΔQ (r=-0.827, p<0.0001) on intact lesions while a weak but suggestive, although non-significant, correlation was identified between average lesion depth and ΔR (r=0.369, p=0.059) and ΔX (r=0.595, p=0.0011). However, the corresponding correlation was not statistically significant, when lesions with surface loss were considered for QLF and MDP measures. CONCLUSIONS: QLF measures ΔF and ΔQ were strongly correlated with lesion depth in lab-simulated lesions with no surface loss, but not among lesions with surface defects. The two MDP-associated measures, ΔR and ΔX, could not be said to differ significantly when lesions with and without surface defects were compared with lesion depth. Because intact lesions can be remineralized, accurate assessment of their status is imperative for caries treatment. CLINICAL SIGNIFICANCE: Dental caries is still widely prevalent today. We now know that with early stage detection, remineralization can be accomplished. Being able to identify dental caries in its reversible stage (before physical surface loss) is paramount for the clinician to be able to treat the disease non-invasively.

Effect of an alcohol-free, 1% chlorhexidine gel as an adjunct to a fluoridated dentifrice using an intraoral crown model.

BACKGROUND/AIMS: The use of chlorhexidine as a topically applied oral antiseptic is well documented; however, clinical studies examining the effects of chlorhexidine gel on in situ dental caries are limited. This study utilized an in situ caries model and a modified crossover design to examine whether the addition of a biweekly topical, alcohol-free, 1% chlorhexidine digluconate gel to a daily fluoridated dentifrice inhibited artificial caries in dental tissues better than the fluoridated dentifrice alone when compared to a nonfluoridated placebo dentifrice. METHODS: Thirty patients were recruited based on their need for a mandibular, full crown. Artificial caries lesions were created in extracted human teeth and enamel and root tissue sections 100 mum in thickness were characterized using polarized light microscopy. The sections were fixed in the crown and placed on the prepared tooth. The participants were assigned a placebo toothpaste, a toothpaste with 1,100 ppm F or a 1,100 ppm F toothpaste followed by 1 ml of 1% chlorhexidine gel at day 1 and day 14 (chlorhexidine+). Patients were instructed to brush twice daily for 4 weeks. Following each round, the sections in the crown were replaced with new sections. The sections were recharacterized and the mean changes were compared using ANOVA at alpha = 0.05. RESULTS: The chlorhexidine + Fdentifrice and the F dentifrice alone significantly reduced lesion area in enamel tissue when compared to the placebo dentifrice. Both treatments also inhibited lesion progression and initiation in root tissue better than control in this model system. Although the chlorhexidine+ group enhanced remineralization and inhibited lesion progression better than the F(-) dentifrice alone for all outcomes measured, the differences were not significant. CONCLUSIONS: The chlorhexidine, in conjunction with a fluoride dentifrice, was no more effective than the fluoride dentifrice alone. Further study is needed before this 1% alcohol-free chlorhexidine gel should be recommended as an adjunct to a fluoride dentifrice in the treatment of dental caries.

Effect of fluoridated milk on progression of root surface lesions in vitro under pH cycling conditions.

The aim of this study was to assess the effect of milk with 0, 2.5 or 5 ppm F on progression and remineralization of caries-like root surface lesions using a pH cycling model. The root surface lesions were created utilizing a partially saturated lactic acid buffer at pH 4.6. Longitudinal sections were cut through the lesion and analyzed using polarized light microscopy (PLM) and microradiography (MRG). The sections were then coated with an acid resistant varnish, except the outer natural surface that would be exposed to water, milk or fluoridated milk and cycled in a de- and remineralizing system for 2 weeks. The lesions were characterized again by PLM and MRG after treatment. A significant reduction in lesion progression was found by PLM and MRG after treatment with either non-fluoridated or fluoridated milk when compared to the control group. Using quantitative MRG, mineral change and distribution in the lesions were recorded. A possible protective effect of fluoridated milk on root surface caries was supported by a reduction in the progression of the lesions and an increase in the mineral within the lesion.

In situ evaluation of sodium hexametaphosphate-containing dentifrices.

The purpose of this investigator-blinded, five-treatment, crossover human intraoral study was to evaluate the effects of two experimental dentifrice formulations containing either stannous fluoride (SnF(2)) or sodium fluoride (NaF) packaged with sodium hexametaphosphate in a dual-phase delivery system on demineralization-remineralization using an in situ model system. The experimental dentifrice formulations' ability to alter demineralization-remineralization was compared to a series of three controls: SnF(2)-positive control, NaF-positive control and no-fluoride placebo-negative control. The single-section crown model, developed at the University of Iowa, was used to assess the fluoride efficacy of two experimental products versus the placebo containing no fluoride and positive controls. The results of the current in situ study suggest a clinical level of anticaries activity for the experimental SnF(2) and NaF dentifrice formulations that was as good as either of the positive controls, when evaluated using polarized light microscopy. This supports the conclusion that the use of the sodium hexametaphosphate ingredient does not interfere with the normal fluoride activity of these toothpastes. In addition, the experimental SnF(2) product was numerically better than both the NaF and placebo controls at preventing demineralization of sound root surfaces.

Linkage assignment of a DNA sequence (ERCC2L1) homologous to a human DNA repair gene in Xiphophorus fishes: implications for the evolutionary derivation of human chromosome 19.

Fish gene mapping studies have identified several syntenic groups showing conservation over more than 400 million years of vertebrate evolution. In particular, Xiphophorus linkage group IV has been identified as a homolog of human chromosomes 15 and 19. During mammalian evolution, loci coding for glucosephosphate isomerase, peptidase D, muscle creatine kinase, and several DNA repair genes (ERCC1, ERCC2, and XRCC1) appear as a conserved syntenic group on human chromosome 19. When X. clemenciae and X. milleri PstI endonuclease-digested genomic DNA was used in Southern analysis with a human ERCC2 DNA repair gene probe, a strongly cross-hybridizing restriction fragment length polymorphism was observed. Backcrosses to X. clemenciae from X. milleri x X. clemenciae F1 hybrids allowed tests for linkage of the ERCC2-like polymorphism to markers covering a large proportion of the genome. Statistically significant evidence for linkage was found only for ERCC2L1 and CKM (muscle creatine kinase), with a total of 41 parents and 2 recombinants (4.7% recombination, chi 2 = 35.37, P less than 0.001); no evidence for linkage to GPI and PEPD in linkage group IV was detected. The human chromosome 19 synteny of ERCC2 and CKM thus appears to be conserved in Xiphophorus, while other genes located nearby on human chromosome 19 are in a separate linkage group in this fish. If Xiphophorus gene arrangements prove to be primitive, human chromosome 19 may have arisen from chromosome fusion or translocation events at some point since divergence of mammals and fishes from a common ancestor.

Assignment of an erbB-like DNA sequence to linkage group VI in fishes of the genus Xiphophorus (Poeciliidae).

The inheritance of 23 protein polymorphisms was compared with the inheritance of a DNA restriction fragment length polymorphism (RFLP) of a strongly cross-hybridizing erbB-related sequence, epidermal growth factor receptor-like-1 (EGFRL1), in Xiphophorus clemenciae X X. milleri-derived backcross hybrids. Two polymorphic bands were noted in this cross with a v-erbB probe after PstI digestion: a 10-kilobase (kb) band in X. clemenciae and a 9-kb band in X. milleri. Joint segregation analysis of the RFLPs and protein polymorphisms indicate that this erbB-related sequence can be assigned to Xiphophorus linkage group VI, which also comprises genes coding for glutamine synthetase (GLNS), nucleoside phosphorylase-2 (NP2), and transferin (TF). We have designated this RFLP as alleles at a locus called EGFRL1 because of very strong cross-hybridization with the v-erbB probe, known to be homologous to the mammalian EGFR gene. This mapping assignment is the first autosomal linkage of an oncogene sequence reported in fish, which provide a large number of genetically controlled experimental tumor models.

Antibody to a human DNA repair protein allows for cloning of a Drosophila cDNA that encodes an apurinic endonuclease.

The cDNA of a Drosophila DNA repair gene, AP3, was cloned by screening an embryonic lambda gt11 expression library with an antibody that was originally prepared against a purified human apurinic-apyrimidinic (AP) endonuclease. The 1.2-kilobase (kb) AP3 cDNA mapped to a region on the third chromosome where a number of mutagen-sensitive alleles were located. The cDNA clone yielded an in vitro translation product of 35,000 daltons, in agreement with the predicted size of the translation product of the only open reading frame of AP3, and identical to the molecular size of an AP endonuclease activity recovered following sodium dodecyl sulfate-polyacrylamide gel electrophoresis of Drosophila extracts. The C-terminal portion of the predicted protein contained regions of presumptive DNA-binding domains, while the DNA sequence at the amino end of AP3 showed similarity to the Escherichia coli recA gene. AP3 is expressed as an abundant 1.3-kb mRNA that is detected throughout the life cycle of Drosophila melanogaster. Another 3.5-kb mRNA also hybridized to the AP3 cDNA, but this species was restricted to the early stages of development.

The use of saturated DCPD in remineralization of artificial caries lesions in vitro.

Dicalcium phosphate dihydrate (DCPD) may play a significant role in the caries lesion since it is a stable calcium phosphate phase under acidic conditions. The reaction of DCPD and fluoride, forming fluorapatite (FAP), may provide a potentially promising treatment regimen for remineralization of caries lesions in vivo. The purpose of this study was to determine whether a two-step DCPD and inorganic wash with fluoride can remineralize artificial caries-like lesions in vitro. We used the single-section technique to facilitate quantitation of the same tissue before and after the experimental regimen. The two-step remineralizing treatment was repeated three times and consisted of a two-minute saturated DCPD treatment (pH 2.1) followed by a 24-hour inorganic wash. Lesion parameters were recorded before and after treatment by the taking of polarized light photomicrographs of each section after imbibition in several media. The changes in the tissue following treatment were expressed as a percent change in the area of the initial pre-treatment lesion. Significant reductions (p < 0.02) in lesion pore volume were observed in all aqueous media examined. In the lesions after imbibition in quinoline, remineralization was also apparent from the significant increase in the area of the dark zone following treatment. This two-step DCPD treatment appears to remineralize artificial caries-like lesions effectively, but additional work is needed to determine whether it affords any protection against subsequent cariogenic challenges.

Development of an intra-oral single-section remineralization model.

An intra-oral model system has been developed which uses a single-section technique for before-and-after measurements on the same tissue. This model allows for placement of sections of enamel at both buccal and approximal sites. These sections may be sound or possess white-spot lesions. This allows for the evaluation of lesion initiation, lesion progression, and/or lesion remineralization. The sections are appropriate for measurement by polarized light microscopy, and, although not included in this study, they are also suitable for microradiographic evaluation. With ten human volunteers, the model system was evaluated by means of three rinse regimens in a cross-over design. The distilled water rinse showed the whole range of possible changes (e.g., demineralization, no change, and remineralization). More consistent remineralization was observed when a fluoride rinse or a remineralizing fluid was used. This model system should prove to be quite useful in evaluation of demineralization and remineralization phenomena in the oral environment.

Intranuclear localization of UV-induced DNA repair in human VA13 cells.

We have investigated the intranuclear localization of DNA-repair synthesis in G1-phase VA13 human cells. Ultraviolet-irradiated cells were permitted to perform unscheduled DNA synthesis in 3H-thymidine (3H-TdR) and then extracted with nonionic detergent and 2 M NaCl to produce nucleoids in which residual nuclear matrix was surrounded by an extended halo of DNA loops. Autoradiographic analysis of these structures permitted discrimination of DNA repair between the matrix and halo regions. Repair label in nucleoids prepared from cells after exposure to fluences of 2.5-30 J/m2 exhibited a dose-dependent association with the nuclear matrix, which ranged from 80% after 2.5 J/m2 to 50% after 30 J/m2. These results support the view that DNA repair is a nuclear matrix-associated process. This conclusion is in agreement with our preliminary study (Harless et al., 1983) and the results of McCready and Cook (1984) but contrasts with that of Mullenders et al. (1983). Questions concerning the differing experimental designs and their potential effects on the localization of DNA repair are discussed. The implications of these results to previous attempts to isolate chromatin factors associated with DNA repair are also considered.

Comparison of artificial white spots by microradiography and polarized light microscopy.

This work compared lesions produced by three artificial caries systems with natural white spot lesions using both polarized light microscopy and microradiography. The three systems employed were the acidified gelatin gel, diphosphonate surface dissolution inhibitor, and a partially saturated buffer system. When we compared the natural white spot lesions with the artificial caries-like lesions, we found that the acidified gel system reproduced the classical histological zones most frequently. All systems showed a radiopaque surface layer overlying a radiolucent body of the lesion. This radiopaque layer could not be equated with the negatively birefringent surface zone seen in polarized light.

Topical fluoride application and lesion progression in vitro.

The objectives of this investigation were to study the effects of topical fluoride application on white spot enamel and the effect that this application would have on a second acid exposure (lesion progression). Artificial white spot lesions of approximately 200 micron were created with an acidified gel technique, central control sections were removed, and the remaining tooth halves were randomly paired, with one half serving as an untreated control while the other received a single four-minute application of 1.23% (w/v) fluoride solution of either NH4F, Na2SnF6, APF, or TiF4. Both tooth halves were sectioned following progression and examined with polarized light microscopy. Lesion depth, internal pore volume, and presence, size and shape of dark zones were determined. The considerable variation among progressed lesions revealed no significant benefit from any topical fluoride treatment.

Endodeoxyribonuclease activity associated with Rauscher murine leukemia virus.

Preparations of purified Rauscher murine leukemia virus were found to contain an endodeoxyribonuclease after disruption of the virus with nonionic detergents. The enzyme makes single-strand breaks in linear or covalently closed circular phage double-stranded DNA molecules. The enzyme was partially purified by ion-exchange chromatography on DEAE- and carboxymethyl-Sepharose columns followed by electrophoresis in DNA-containing polyacrylamide gels. The enzyme was separated from reverse transcriptase (p80pol), and the final endonuclease preparation contained no detectable reverse transcriptase activity. The DEAE-Sepharose column-purified endonuclease activity contained a polypeptide of about 40,000 Mr that we term p40. Peptide mapping experiments demonstrated that p40 shares methionine-labeled tryptic peptides with Pr200gag-pol and Pr135pol. Six major methionine-labeled tryptic peptides derived from p40 were found in Pr200gag-pol, but only five of these were detected in Pr135pol. The four core proteins (p30, p15, pp12, and p10) and p80pol plus p40 account for most, but not all, of the peptide sequences of Pr200gag-pol. The endonuclease-associated p40 is similar in size and precursor origin to the avian retrovirus-coded endonuclease (p32). In view of these similarities to the avian p32 endonuclease and its association with partially purified Rauscher murine leukemia virus-associated endonuclease preparations, we propose that p40 is the Rauscher murine leukemia virus-coded endonuclease.