Proportioning variability in the dispensation of hand-mixed dental cements

Objectives: The purpose of this investigation was to determine for dispensed multiples (1 through 4) of powder (P) and liquid (L) in hand-mixed dental cement whether: (1) the mean (P/L) ratio (m/m) and (2) the maximum difference in (P/L) ratio is dependent on the number of multiples dispensed. The Null hypotheses were: (a) mean (P/L) ratio is independent of the number of multiples dispensed and (b) maximum difference in (P/L) ratio is independent of the number of multiples dispensed.
Methods: The materials investigated are listed in the Table. The masses of dispensed aliquots of powder and liquid were measured by a single operator (n=10, for multiples 1 through 4) on a 4-place analytical balance. All measurements were made independently and all possible (P/L) ratios calculated for each sample. The effect of multiple dispensations on (P/L) ratios and maximum (P/L) differences was by one-way ANOVA and linear regression, respectively, with the Tukey post-hoc correction for multiple comparisons.MULTIPLE DISPENSEDDISPENSED MU(x1)(x2)(x3)(x4)Zinc phosphateHeraeus12.271(0.691)a13.051(1.269)b13.215(0.824)b13.118(1.149)bFuji IXGC4.209(0.373)a4.085(0.275)b4.095(0.226)b4.095(0.217)bIRMDentsply7.933(0.767)a7.430(0.451)b7.977(0.729)a8.186(0.929)aKetac-Cem3M Espe9.6206(0.613)a9.714(0.523)a9.298(0.314)b9.321(0.292)bMean (SD) powder/liquid ratio (m/m). Superscript letters represent significances (α = 0.05) within each material
Results: Mean (SD) (P/L) ratios are presented in the Table. Null hypothesis (a) is rejected: either (x1) or (x2) dispensation yields a different (P/L) ratio to (x3) or (x4) (p < 0.05). Null hypothesis (b) is rejected: a negative correlation is observed in max (P/L) ratio difference with dispensed multiple for Ketac Cem (p = 0.029).
Conclusion: For hand-mixed dental cements: (1) more consistent (P/L) ratios may be observed with multiple dispensations of powder & liquid; (2) maximum differences in (P/L) ratio may be negatively correlated with dispensation multiple in some materials.

Solubility parameter based screening methods for early stage formulation development of itraconazole amorphous solid dispersions

Objectives: This article uses conventional and newly extended solubility parameter (δ) methods to identify polymeric materials capable of forming amorphous dispersions with itraconazole (itz). Methods: Combinations of itz and Soluplus, Eudragit E PO (EPO), Kollidon 17PF (17PF) or Kollidon VA64 (VA64) were prepared as amorphous solid dispersions using quench cooling and hot melt extrusion. Storage stability was evaluated under a range of conditions using differential scanning calorimetry and powder X-ray diffraction. Key findings: The rank order of itz miscibility with polymers using both conventional and novel δ-based approaches was 17PF > VA64 > Soluplus > EPO, and the application of the Flory–Huggins lattice model to itz–excipient binary systems corroborated the findings. The solid-state characterisation analyses of the formulations manufactured by melt extrusion correlated well with pre-formulation screening. Long-term storage studies showed that the physical stability of 17PF/vitamin E TPGS–itz was poor compared with Soluplus and VA64 formulations, and for EPO/itz systems variation in stability may be observed depending on the preparation method. Conclusion: Results have demonstrated that although δ-based screening may be useful in predicting the initial state of amorphous solid dispersions, assessment of the physical behaviour of the formulations at relevant temperatures may be more appropriate for the successful development of commercially acceptable amorphous drug products.

Comparative Study of Different Methods for the Prediction of Drug− Polymer Solubility

In this study, a comparison of different methods to predict drug−polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug−polymer solubility at 25 °C was predicted using the Flory−Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine−PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug−polymer solubility.

The Use of High Surface Area Silica and Supercritical Carbon Dioxide to Enhance Solubility of Poorly Water-Soluble Drugs

Purpose Poor water-solubility of BCS class II drugs can limit their commercialization because of reduced oral bioavailability. It has been reported that loading of drug by adsorption onto porous silica would enhance drug solubility due to the increased surface area available for solvent diffusion. In this work, solid dispersions are formed using supercritical carbon dioxide (scCO2). The aim of this research was to characterise the solid-state properties of scCO2 dispersion and to investigate the impact of altering scCO2 processing conditions on final amorphous product performance that could lead to enhancement of drug dissolution rate for BCS class II drugs. Methods Indomethacin (IND) was purchased from Sigma-Aldrich (Dorset, UK) and was used as a model drug with two grades of high surface area silica (average particle sizes 3&[micro] and 7&[micro]), which were obtained directly from Grace-Davison (Germany). Material crystallinity was evaluated using powder X-ray diffraction (PXRD, Rigaku™, miniflex II, Japan) and high-speed differential scanning calorimetry (Hyper-DSC 8000, Perkin Elmer, USA). Materials were placed in a high-pressure vessel consisting of a CO2 cylinder, a Thar™ Technologies P50 high-pressure pump and a 750 ml high-pressure vessel (Thar, USA). Physical mixtures were exposed to CO2 gas above its critical conditions. SEM imaging and elemental analysis were conducted using a Jeol 6500 FEGSEM (Advanced MicroBeam Inc., Austria). Drug release was examined using USP type II dissolution tester (Caleva™, UK). Results The two grades of silica were found to be amorphous using PXRD and Hyper-DSC. Using PXRD, it was shown that an increase in incubation time and pressure resulted in a decrease in the crystalline content. Drug release profiles from the two different silica formulations prepared under the same conditions are shown in Figure 1. It was found that there was a significant enhancement in drug release, which was influenced, by silica type and other experiment conditions such as temperature, pressure and exposure time. SEM imaging and elemental analysis showed drug deposited inside silica pores as well as on the outer surface. Conclusion This project has shown that silica carrier platforms may be used as an alternative approach to generating polymeric solid dispersions of amorphous drugs exhibiting enhanced solubility.

Quality of reporting of dental survival analyses

To explore the quality of reporting (writing and graphics) of articles that used time-to-event analyses to report dental treatment outcomes. A systematic search of the top 50 dental journals in 2008 produced the sample of articles for this analysis. Articles reporting treatment outcomes with (n = 95) and without (n = 91) time-to-event statistics were reviewed. Survival descriptive words used in the two groups were analysed (Pearson's chi-square). The quality of life tables, survival curves and time-to-event statistics were assessed (Kappa analysed agreement) and explored. Words describing dental outcomes 'over time' were more common in time-to-event compared with control articles (77%, 3%, P < 0.001). Non-specific use of 'rate' was common across both groups. Life tables and survival curves were used by 39% and 48% of the time-to-event articles, with at least one used by 82%. Construction quality was poor: 21% of life tables and 28% of survival curves achieved an acceptable standard. Time-to-event statistical reporting was poor: 3% achieved a high and 59% achieved an acceptable standard. The survival statistic, summary figure and standard error were reported in 76%, 95% and 20% of time-to-event articles. Individual statistical terms and graphic aids were common within and unique to time-to-event articles. Unfortunately, important details were regularly omitted from statistical descriptions and survival figures making the overall quality poor. It is likely this will mean such articles will be incorrectly indexed in databases, missed by searchers and unable to be understood completely if identified.

Accuracy of medical subject heading indexing of dental survival analyses

PURPOSE: To assess the Medical Subject Headings (MeSH) indexing of articles that employed time-to-event analyses to report outcomes of dental treatment in patients.

MATERIALS AND METHODS: Articles published in 2008 in 50 dental journals with the highest impact factors were hand searched to identify articles reporting dental treatment outcomes over time in human subjects with time-to-event statistics (included, n = 95), without time-to-event statistics (active controls, n = 91), and all other articles (passive controls, n = 6,769). The search was systematic (kappa 0.92 for screening, 0.86 for eligibility). Outcome-, statistic- and time-related MeSH were identified, and differences in allocation between groups were analyzed with chi-square and Fischer exact statistics.

RESULTS: The most frequently allocated MeSH for included and active control articles were "dental restoration failure" (77% and 52%, respectively) and "treatment outcome" (54% and 48%, respectively). Outcome MeSH was similar between these groups (86% and 77%, respectively) and significantly greater than passive controls (10%, P < .001). Significantly more statistical MeSH were allocated to the included articles than to the active or passive controls (67%, 15%, and 1%, respectively, P < .001). Sixty-nine included articles specifically used Kaplan-Meier or life table analyses, but only 42% (n = 29) were indexed as such. Significantly more time-related MeSH were allocated to the included than the active controls (92% and 79%, respectively, P = .02), or to the passive controls (22%, P < .001).

CONCLUSIONS: MeSH allocation within MEDLINE to time-to-event dental articles was inaccurate and inconsistent. Statistical MeSH were omitted from 30% of the included articles and incorrectly allocated to 15% of active controls. Such errors adversely impact search accuracy.

Will your article be found? Authors choose a confusing variety of words to describe dental survival analyses

OBJECTIVES: Identify the words and phrases that authors used to describe time-to-event outcomes of dental treatments in patients.

MATERIALS AND METHODS: A systematic handsearch of 50 dental journals with the highest Citation Index for 2008 identified articles reporting dental treatment with time-to-event statistics (included "case" articles, n = 95), without time-to-event statistics (active "control" articles, n = 91), and all other articles (passive "control" articles n = 6796). The included and active controls were read, identifying 43 English words across the title, aim and abstract, indicating that outcomes were studied over time. Once identified, these words were sought within the 6796 passive controls. Words were divided into six groups. Differences in use of words were analyzed with Pearson's chi-square across these six groups, and the three locations (title, aim, and abstract).

RESULTS: In the abstracts, included articles used group 1 (statistical technique) and group 2 (statistical terms) more frequently than the active and passive controls (group 1: 35%, 2%, 0.37%, P < 0.001 and group 2: 31%, 1%, 0.06%, P < 0.001). The included and active controls used group 3 (quasi-statistical) equally, but significantly more often than the passive controls (82%, 78%, 3.21%, P < 0.001). In the aims, use of target words was similar for included and active controls, but less frequent for groups 1-4 in the passive controls (P < 0.001). In the title, group 2 (statistical techniques) and groups 3-5 (outcomes) were similar for included and active controls, but groups 2 and 3 were less frequent in the passive controls (P < 0.001). Significantly more included articles used group 6 words (stating the study duration) (54%, 30%, P = 0.001).

CONCLUSION: All included articles used time-to-event analyses, but two-thirds did not include words to highlight this in the abstract. There is great variation in the words authors used to describe dental time-to-event outcomes. Electronic identification of such articles would be inconsistent, with low sensitivity and specificity. Authors should improve the reporting quality. Journals should allow sufficient space in abstracts to summarize research, and not impose unrealistic word limits. Readers should be mindful of these problems when searching for relevant articles. Additional research is required in this field.

A systematic review and meta-analysis of the survival of feldspathic porcelain veneers over 5 and 10 years

PURPOSE: This systematic review reports on the survival of feldspathic porcelain veneers.

MATERIALS AND METHODS: The Cochrane Library, MEDLINE (OVID), Embase, Web of Knowledge, selected journals, clinical trials registers, and conference proceedings were searched independently by two reviewers. Academic colleagues were also contacted to identify relevant research. Inclusion criteria were human cohort studies (prospective and retrospective) and controlled trials assessing outcomes of feldspathic porcelain veneers in more than 15 patients and with at least some of the veneers in situ for 5 years. Of 4,294 articles identified, 116 studies underwent full-text screenings and 69 were further reviewed for eligibility. Of these, 11 were included in the qualitative analysis and 6 (5 cohorts) were included in meta-analyses. Estimated cumulative survival and standard error for each study were assessed and used for meta-, sensitivity, and post hoc analyses. The I2 statistic and the Cochran Q test and its associated P value were used to evaluate statistical heterogeneity, with a random-effects meta-analysis used when the P value for heterogeneity was less than .1. Galbraith, forest, and funnel plots explored heterogeneity, publication patterns, and small study biases.

RESULTS: The estimated cumulative survival for feldspathic porcelain veneers was 95.7% (95% confidence interval [CI]: 92.9% to 98.4%) at 5 years and ranged from 64% to 95% at 10 years across three studies. A post hoc meta-analysis indicated that the 10-year best estimate may approach 95.6% (95% CI: 93.8% to 97.5%). High levels of statistical heterogeneity were found.

CONCLUSIONS: When bonded to enamel substrate, feldspathic porcelain veneers have a very high 10-year survival rate that may approach 95%. Clinical heterogeneity is associated with differences in reported survival rates. Use of clinically relevant survival definitions and careful reporting of tooth characteristics, censorship, clustering, and precise results in future research would improve metaanalytic estimates and aid treatment decisions.

Pre-Radiotherapy Dental Assessment of Head and Neck Oncology Patients: An Audit.

Objectives: Approximately 300 people are diagnosed with Head and Neck cancer annually in Northern Ireland. The management may include treatment by surgery or by chemotherapy and radiotherapy,
or a combination of modalities. Patients whose oral cavity, teeth, salivary glands and jaws that
will be affected by treatment, particularly radiotherapy should have a pre-treatment assessment. This should be done as early as possible to maximise the time available for dental management. However, this can be challenging owing to the complexities of cancer diagnosis, treatment planning and multidisciplinary management. At the Belfast Dental Hospital, a number of patients were referred post- radiotherapy with complications after not having received a pre-treatment assessment. The referrals for pre- treatment dental assessment were also late in patients’ multidisciplinary journey, limiting the time period
for dental input. The purpose of this audit was to examine the time period between dental assessment and commencement of radiotherapy and whether this was an adequate time frame for dental management. This audit will also examine the dental diseases present and the treatments required pre-radiotherapy. Methods: Data for this audit was collected over 4 months in 2012
by analysing the dental charts and referrals of new patients who were referred to and attended the dental head and neck oncology clinic. A standardised referral pro-forma was introduced from September 2013 to improve the referral process.
A re-audit was conducted over 4 months in 2014. Data was collected similarly as previous. The time period between dental assessment and commencement of radiotherapy was examined. The presence of dental disease and subsequent treatments required were also noted.
Results: 63 new patients were examined in the dental head and neck oncology clinic over 4 months in 2012. 48 (76.2%) were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 11 days. A new standardised referral pro-forma was introduced in 2013. In the re-audit, 65 new patients were seen over 4 months in 2014.
60 (92.3%) patients were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 18 days.
Conclusion: Given the high prevalence of pre-existing dental disease amongst head and neck cancer patients, prompt dental assessment and treatment is vital. Efforts aimed at improving the care pathway are on-going through the implementation of a mandatory referral pro-forma and a dedicated assessment clinic.

A differential protein solubility approach for the depletion of highly abundant proteins in plasma using ammonium sulfate

Depletion of highly abundant proteins is an approved step in blood plasma analysis by mass spectrometry (MS). In this study, we explored a precipitation and differential protein solubility approach as a fractionation strategy for abundant protein removal from plasma. Total proteins from plasma were precipitated with 90% saturated ammonium sulfate, followed by differential solubilization in 55% and 35% saturated ammonium sulfate solutions. Using a four hour liquid chromatography (LC) gradient and an LTQ-Orbitrap XL mass spectrometer, a total of 167 and 224 proteins were identified from the 55% and 35% ammonium sulfate fractions, whereas 235 proteins were found in the remaining protein fractions with at least two unique peptides. SDS-PAGE and exclusive total spectrum counts from LC-MS/MS analyses clearly showed that majority of the abundant plasma proteins were solubilized in 55% and 35% ammonium sulfate solutions, indicating that the remaining protein fraction is of potential interest for identification of less abundant plasma proteins. Serum albumin, serotransferrin, alpha-1-antitrypsin and transthyretin were the abundant proteins that were highly enriched in 55% ammonium sulfate fractions. Immunoglobulins, complement system proteins, and apolipoproteins were among other abundant plasma proteins that were enriched in 35% ammonium sulfate fractions. In the remaining protein fractions a total of 40 unique proteins were identified of which, 32 proteins were identified with at least 10 exclusive spectrum counts. According to PeptideAtlas, 9 of these 32 proteins were estimated to be present at low μg ml(-1) (0.12-1.9 μg ml(-1)) concentrations in the plasma, and 17 at low ng ml(-1) (0.1-55 ng ml(-1)) range.

Comparison of Composite Placement Techniques by Recently Qualified Dental Practitioners.

Objectives: To evaluate the placement of composite materials by new graduates using three alternative placement techniques.Methods: A cohort of 34 recently qualified graduates were asked to restore class II interproximal cavities in plastic teeth using three different techniques.

(i) A conventional incremental filling technique (Herculite XRV) using increments no larger than 2-mm with an initial layer on the cervical floor of the box of 1-mm.
(ii) Flowable bulk fill technique (Dentsply SDR) bulk fill placement in a 3-mm layer followed by an incremental fill of a microhybrid resin
(iii) Bulk fill (Kerr Sonicfill) which involved restorations placed in a 5-mm layer.

The operators were instructed in each technique, didactically and with a hands-on demonstration, prior to restoration placement.
All restorations were cured according to manufacturer’s recommendations. Each participant restored 3 teeth, 1 tooth per treatment technique.
The restorations were evaluated using modified USPHS criteria to assess both the marginal adaptation and the surface texture of the restorations. Blind evaluations were carried out independently by two examiners with the aid of magnification (loupes X2.5). Examiners were standardized prior to evaluation.
Results: Gaps between the tooth margins and the restoration or between the layers of the restoration were found in 13 of Group (i), 3 of Group (ii), and 4 of Group (iii)
Statistical analysis revealed a significant difference between the incrementally filled group (i) and the flowable bulk-fill group (ii) (p=0.0043) and between the incrementally filled (i) and the bulk fill groups (iii) (p=0.012) and no statistical difference (p=0.69) between the bulk filled groups Conclusions: Bulk fill techniques may result in a more satisfactory seal of the cavity margins when restoring with composite.

Identification of novel Factor XI mutations in a patient requiring dental extractions

Factor XI is a serine protease that participates in the intrinsic pathway of blood coagulation. Patients deficient in factor XI exhibit varying degrees of post operative bleeding following invasive surgical procedures such as dental extractions. Objectives: The aim of the study was to identify the specific mutations in a patient from a family with known factor XI deficiency. Methods: Samples were obtained from the patient, his mother and his father and subjected to DNA sequencing. Each protein coding exon 2-15 of the factor XI gene was amplified by polymerase chain reaction (PCR) followed by bidirectional sequencing utilizing di-deoxy chain termination chemistry. Results: The patient had a factor XI level of 20% of normal. Initial sequencing of factor XI from the patient identified a point mutation (646G>A) and a putative splice site mutation (1567+4A>T) in intron 13. These are novel previously unreported mutations. DNA sequence analysis of the mother revealed the 1567+4A>T mutation and the father exhibited the 646G>A mutation. As a consequence the treatment proceeded without serious bleeding complication and required administration only of transexamic acid though factor XI was available as haemostatic cover. Conclusion: The two mutations identified in this family are novel; further laboratory investigation of the functional consequences of those mutations is currently underway. Although factor XI deficiency is rare in the Northern Irish population this study highlights the techniques available to sequence and analyse this and similar haematological disorders.

Impact of Referral Protocols on the Dental Management of Patients Undergoing Treatment for Head and Neck Oncology in Northern Ireland

Objective: To evaluate the handling, by a group of practice-based researchers, of a recently introduced bulk fill resin-based composite restorative material, Filtek Bulk Fill Restorative (3M ESPE).

Methods: The twelve selected evaluators were sent explanatory letters, a pack of the material under investigation to use for 8 weeks, and a questionnaire.

Results: The evaluators rated the ease of use of the bulk fill restorative the same as the previously used posterior composite material. The provision of one shade only for evaluation may have compromised the score for aesthetic quality. No post-operative sensitivity was reported.

Conclusions: The bulk fill material was well received as indicated by the high number of evaluators who would both purchase the material and recommend it to colleagues.

Clinical relevance: A recently introduced bulk fill restorative material achieved a rating for handling which was similar to the evaluators’ previously used resin composite, although there were some concerns regarding the translucency of the material.

NPY Y1 and VPAC1 receptor expression in human dental pulps

Neuropeptides such as neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) have been shown by our research group to be present in human dental pulp tissue. Neuropeptides cannot cross cell membranes and therefore to exert their biological effects they must bind to selected receptors on the surface of target cell membranes. However, the expression of receptor proteins for NPY and/or VIP have yet to be reported in human pulp tissue. The presence of neuropeptide receptors can be conveniently determined by Western blotting using specific anti-receptor antibodies. Objectives: The aim of this work was to identify the presence of the NPY Y1 receptor and the VIP receptor VPAC1 in human dental pulp tissue from both intact and carious teeth using Western blotting. Methods: Pulp tissue was collected from both intact and carious teeth and membrane preparations from these tissues were then subject to sodium dodecyl sulphate gel electrophoresis (SDS-PAGE), transferred to nitrocellulose and probed with specific antibodies to either the NPY Y1 receptor or the VPAC1 receptor. Results: Individual Western blotting experiments revealed the presence of immunoreactive bands corresponding to the known molecular weights of the NPY Y1 and VPAC1 receptor proteins in both intact and carious pulp samples. Conclusions: Demonstration of the presence of NPY Y1 and VPAC1 receptor protein expression in pulpal tissue from intact and carious teeth provides further support for the roles of these neuropeptides in pulpal health and disease.