How vague is vague? How informative is informative? Reference analysis for Bayesian meta-analysis.

Meta-analysis provides important insights for evidence-based medicine by synthesizing evidence from multiple studies which address the same research question. Within the Bayesian framework, meta-analysis is frequently expressed by a Bayesian normal-normal hierarchical model (NNHM). Recently, several publications have discussed the choice of the prior distribution for the between-study heterogeneity in the Bayesian NNHM and used several "vague" priors. However, no approach exists to quantify the informativeness of such priors, and thus, we develop a principled reference analysis framework for the Bayesian NNHM acting at the posterior level. The posterior reference analysis (post-RA) is based on two posterior benchmarks: one induced by the improper reference prior, which is minimally informative for the data, and the other induced by a highly anticonservative proper prior. This approach applies the Hellinger distance to quantify the informativeness of a heterogeneity prior of interest by comparing the corresponding marginal posteriors with both posterior benchmarks. The post-RA is implemented in the freely accessible R package ra4bayesmeta and is applied to two medical case studies. Our findings show that anticonservative heterogeneity priors produce platykurtic posteriors compared with the reference posterior, and they produce shorter 95% credible intervals (CrI) and optimistic inference compared with the reference prior. Conservative heterogeneity priors produce leptokurtic posteriors, longer 95% CrI and cautious inference. The novel post-RA framework could support numerous Bayesian meta-analyses in many research fields, as it determines how informative a heterogeneity prior is for the actual data as compared with the minimally informative reference prior.

Teaching: confidence, prediction and tolerance intervals in scientific practice: a tutorial on binary variables.

BACKGROUND: One of the emerging themes in epidemiology is the use of interval estimates. Currently, three interval estimates for confidence (CI), prediction (PI), and tolerance (TI) are at a researcher's disposal and are accessible within the open access framework in R. These three types of statistical intervals serve different purposes. Confidence intervals are designed to describe a parameter with some uncertainty due to sampling errors. Prediction intervals aim to predict future observation(s), including some uncertainty present in the actual and future samples. Tolerance intervals are constructed to capture a specified proportion of a population with a defined confidence. It is well known that interval estimates support a greater knowledge gain than point estimates. Thus, a good understanding and the use of CI, PI, and TI underlie good statistical practice. While CIs are taught in introductory statistical classes, PIs and TIs are less familiar. RESULTS: In this paper, we provide a concise tutorial on two-sided CI, PI and TI for binary variables. This hands-on tutorial is based on our teaching materials. It contains an overview of the meaning and applicability from both a classical and a Bayesian perspective. Based on a worked-out example from veterinary medicine, we provide guidance and code that can be directly applied in R. CONCLUSIONS: This tutorial can be used by others for teaching, either in a class or for self-instruction of students and senior researchers.

Retention force of polyetheretherketone and cobalt-chrome-molybdenum removable dental prosthesis clasps after artificial aging.

OBJECTIVES: To examine the retention force of removable dental prosthesis (RDP) clasps made from polyetheretherketone (PEEK) and cobalt-chrome-molybdenum (CoCrMo, control group) after storage in water and artificial aging. MATERIALS AND METHODS: For each material, 15 Bonwill clasps with retentive buccal and reciprocal lingual arms situated between the second pre- and first molar were manufactured by milling (Dentokeep [PEEKmilled1], NT digital implant technology; breCAM BioHPP Blank [PEEKmilled2], bredent), pressing (BioHPP Granulat for 2 press [PEEKpressed], bredent), or casting (remanium GM 800+ [CoCrMo], Dentaurum); N = 60, n = 15/subgroup. A total of 50 retention force measurements were performed for each specimen per aging level (initial; after storage [30 days, 37 °C] and 10,000 thermal cycles; after storage [60 days, 37 °C] and 20,000 thermal cycles) in a pull-off test. Data were statistically analyzed using one-way ANOVA, post hoc Scheffé and mixed models (p < 0.05). RESULTS: Initial, PEEKpressed (80.2 ± 35.2) and PEEKmilled1 (98.9 ± 40.3) presented the lowest results, while PEEKmilled2 (170.2 ± 51.8) showed the highest values. After artificial aging, the highest retention force was observed for the control group (131.4 ± 56.8). The influence of artificial aging was significantly higher for PEEK-based materials. While PEEKmilled2 and PEEKpressed showed an initial decline in retention force, all other groups presented no impact or an increase in retention force over a repetitive insertion and removal of the clasps. CONCLUSIONS: Within the tested PEEK materials, PEEKmilled2 presented superior results than PEEKpressed. Although CoCrMo showed higher values after artificial aging, all materials exhibited sufficient retention to recommend usage under clinical conditions. CLINICAL RELEVANCE: As RDPs are still employed for a wide range of indications, esthetic alternatives to conventional CoCrMo clasps are sought.

Is the high-performance thermoplastic polyetheretherketone indicated as a clasp material for removable dental prostheses?

OBJECTIVES: To investigate the retention force of polyetheretherketone (PEEK) removable dental prosthesis clasps in comparison with a cobalt-chrome-molybdenum control group after storage in artificial saliva. MATERIALS AND METHODS: Clasps were milled (Dentokeep (PEEKmilled1), NT digital implant technology; breCAM BioHPP Blank (PEEKmilled2), bredent), pressed (BioHPP Granulat for 2 press (PEEKpressed), bredent), or cast (remanium GM 800+ (cobalt-chrome-molybdenum), Dentaurum); N = 60, n = 15/subgroup. Retention force was examined 50 times/specimen in a pull-off test using the universal testing machine (Zwick 1445), where pull-off force was applied with a crosshead speed of 5 mm/minute until the maximum force dropped by 10%, at different aging levels: (1) initial, after storage in artificial saliva for (2) 90 and (3) 180 days. Statistical analysis was performed using one-way ANOVA followed by post hoc Scheffé-test and mixed models (p < 0.05). RESULTS: Cobalt-chrome-molybdenum presented the highest retention force. No differences were observed between polyetheretherketone materials. Cobalt-chrome-molybdenum showed a significant decrease of its values after artificial aging, while polyetheretherketone materials presented similar results over the course of aging. Regarding a repetitive insertion and removal, even though PEEKmilled2 and cobalt-chrome-molybdenum showed an initial increase, ultimately, a decrease in retention force was observed for all tested groups. CONCLUSIONS: Although the control group showed significantly higher results, the retention force of polyetheretherketone materials indicate a potential clinical application. Neither the manufacturing process nor artificial aging showed an impact on the retention force of polyetheretherketone clasps. CLINICAL RELEVANCE: Mechanical properties of novel removable dental prosthesis clasp materials devised to meet the growing esthetic demands of patients need to be investigated to ensure a successful long-term clinical application.

Sensitivity and identification quantification by a relative latent model complexity perturbation in Bayesian meta-analysis.

In recent years, Bayesian meta-analysis expressed by a normal-normal hierarchical model (NNHM) has been widely used for combining evidence from multiple studies. Data provided for the NNHM are frequently based on a small number of studies and on uncertain within-study standard deviation values. Despite the widespread use of Bayesian NNHM, it has always been unclear to what extent the posterior inference is impacted by the heterogeneity prior (sensitivity S ) and by the uncertainty in the within-study standard deviation values (identification I ). Thus, to answer this question, we developed a unified method to simultaneously quantify both sensitivity and identification ( S - I ) for all model parameters in a Bayesian NNHM, based on derivatives of the Bhattacharyya coefficient with respect to relative latent model complexity (RLMC) perturbations. Three case studies exemplify the applicability of the method proposed: historical data for a conventional therapy, data from which one large study is first included and then excluded, and two subgroup meta-analyses specified by their randomization status. We analyzed six scenarios, crossing three RLMC targets with two heterogeneity priors (half-normal, half-Cauchy). The results show that S - I explicitly reveals which parameters are affected by the heterogeneity prior and by the uncertainty in the within-study standard deviation values. In addition, we compare the impact of both heterogeneity priors and quantify how S - I values are affected by omitting one large study and by the randomization status. Finally, the range of applicability of S - I is extended to Bayesian NtHM. A dedicated R package facilitates automatic S - I quantification in applied Bayesian meta-analyses.

Effects of suboptimal adherence of CPAP therapy on symptoms of obstructive sleep apnoea: a randomised, double-blind, controlled trial.

INTRODUCTION: Continuous positive airway pressure (CPAP) is currently the treatment of choice for sleepiness in patients with obstructive sleep apnoea (OSA); however, adherence is often thought to be suboptimal. We investigated the effects of suboptimal CPAP usage on objective and subjective sleepiness parameters in patients with OSA. MATERIAL AND METHODS: In this 2-week, parallel, double-blind, randomised controlled trial we enrolled moderate-to-severe OSA patients with excessive pre-treatment daytime sleepiness (Epworth sleepiness scale (ESS) score >10 points) who had suboptimal CPAP adherence over ≥12 months (mean nightly usage time 3-4 h). Patients were allocated through minimisation to either subtherapeutic CPAP ("sham CPAP") or continuation of CPAP ("therapeutic CPAP"). A Bayesian analysis with historical priors calculated the posterior probability of superiority. RESULTS: Between May, 2016 and November, 2018, 57 patients (aged 60±8 years, 79% male, 93% Caucasian) were allocated in total, and 52 who completed the study (50% in each arm) were included in the final analysis. The unadjusted ESS score increase was 2.4 points (95% CI 0.6-4.2, p=0.01) in the sham-CPAP group when compared to continuing therapeutic CPAP. The probability of superiority of therapeutic CPAP over sham CPAP was 90.4% for ESS, 90.1% for systolic blood pressure and 80.3% for diastolic blood pressure. CONCLUSIONS: Patients with moderate-to-severe OSA and daytime sleepiness are still getting a substantial benefit from suboptimal CPAP adherence, albeit not as much as they might get if they adhered more. Whether a similar statement can be made for even lower adherence levels remains to be established in future trials.

Medication as a risk factor for hospitalization due to heart failure and shock: a series of case-crossover studies in Swiss claims data.

PURPOSE: Heart failure is among the leading causes for hospitalization in Europe. In this study, we evaluate potential precipitating factors for hospitalization for heart failure and shock. METHODS: Using Swiss claims data (2014-2015), we evaluated the association between hospitalization for heart failure and shock, and prescription of oral potassium supplements, non-steroidal anti-inflammatory drugs (NSAIDs), and amoxicillin/clavulanic acid. We conducted case-crossover analyses, where exposure was compared for the hazard period and the primary control period (e.g., 1-30 days before hospitalization vs. 31-60 days, respectively). Conditional logistic regression was applied and subsequently adjusted for addressing potential confounding by disease progression. Sensitivity analyses were conducted and stratification for co-medication was performed. RESULTS: We identified 2185 patients hospitalized with heart failure or shock. Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid was significantly associated with an increased risk for hospitalization for heart failure and shock with crude odds ratios (OR) of 2.04 for potassium (95% CI 1.24-3.36, p = 0.005, 30 days), OR 1.8 for NSAIDs (95% CI 1.39-2.33, p < 0.0001, 30 days), and OR 3.25 for amoxicillin/clavulanic acid (95% CI 2.06-5.14, p < 0.0001, 15 days), respectively. Adjustment attenuated odds ratios, while the significant positive association remained (potassium OR 1.70 (95% CI 1.01-2.86, p = 0.046), NSAIDs OR 1.50 (95% CI 1.14-1.97, p = 0.003), and amoxicillin/clavulanic acid OR 2.26 (95% CI 1.41-3.62, p = 0.001). CONCLUSION: Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid is associated with increased risk for hospitalization. Underlying conditions such as pain, electrolyte imbalances, and infections are likely contributing risk factors. Physicians may use this knowledge to better identify patients at risk and adapt patient management.

Tailored immunosuppression after kidney transplantation - a single center real-life experience.

BACKGROUND: Kidney allograft survival continuously improved with introduction of novel immunosuppressants. However, also immunologically challenging transplants (blood group incompatibility and sensitized recipients) increase. Between 2006 and 2008, a new tailored immunosuppression scheme for kidney transplantation was implemented at the University Hospital in Zurich, together with an ABO-incompatible transplant program and systematic pre- and posttransplant anti-human leukocyte antigen (HLA) antibody screening by Luminex technology. This study retrospectively evaluated the results of this tailored immunosuppression approach with a particular focus on immunologically higher risk transplants. METHODS: A total of 204 consecutive kidney transplantations were analyzed, of whom 14 were ABO-incompatible and 35 recipients were donor-specific anti-HLA antibodies (DSA) positive, but complement-dependent cytotoxicity crossmatch (CDC-XM) negative. We analyzed patient and graft survival, acute rejection rates and infectious complications in ABO-compatible versus -incompatible and in DSA positive versus negative patients and compared those with a historical control group. RESULTS: Overall patient, death-censored allograft survival and non-death-censored allograft survival at 4 years were 92, 91 and 87%, respectively. We found that (1) there were no differences between ABO-compatible and -incompatible and between DSA positive and DSA negative patients concerning acute rejection rate and graft survival; (2) compared with the historical control group there was a significant decrease of acute rejection rates in sensitized patients who received an induction with thymoglobulin; (3) there was no increased rate of infection among the patients who received induction with thymoglobulin compared to no induction therapy. CONCLUSIONS: We observed excellent overall mid-term patient and graft survival rates with our tailored immunosuppression approach. Induction with thymoglobulin was efficient and safe in keeping rejection rates low in DSA positive patients with a negative CDC-XM.

Prediction of health care expenditure increase: how does pharmacotherapy contribute?

BACKGROUND: Rising health care costs are a major public health issue. Thus, accurately predicting future costs and understanding which factors contribute to increases in health care expenditures are important. The objective of this project was to predict patients healthcare costs development in the subsequent year and to identify factors contributing to this prediction, with a particular focus on the role of pharmacotherapy. METHODS: We used 2014-2015 Swiss health insurance claims data on 373'264 adult patients to classify individuals' changes in health care costs. We performed extensive feature generation and developed predictive models using logistic regression, boosted decision trees and neural networks. Based on the decision tree model, we performed a detailed feature importance analysis and subgroup analysis, with an emphasis on drug classes. RESULTS: The boosted decision tree model achieved an overall accuracy of 67.6% and an area under the curve-score of 0.74; the neural network and logistic regression models performed 0.4 and 1.9% worse, respectively. Feature engineering played a key role in capturing temporal patterns in the data. The number of features was reduced from 747 to 36 with only a 0.5% loss in the accuracy. In addition to hospitalisation and outpatient physician visits, 6 drug classes and the mode of drug administration were among the most important features. Patient subgroups with a high probability of increase (up to 88%) and decrease (up to 92%) were identified. CONCLUSIONS: Pharmacotherapy provides important information for predicting cost increases in the total population. Moreover, its relative importance increases in combination with other features, including health care utilisation.

Bonding to new CAD/CAM resin composites: influence of air abrasion and conditioning agents as pretreatment strategy.

OBJECTIVES: Because of their industrially standardized process of manufacturing, CAD/CAM resin composites show a high degree of conversion, making a reliable bond difficult to achieve. PURPOSE: The purpose of this experiment was to investigate the tensile bond strength (TBS) of luting composite to CAD/CAM resin composite materials as influenced by air abrasion and pretreatment strategies. MATERIAL AND METHODS: The treatment factors of the present study were (1) brand of the CAD/CAM resin composite (Brilliant Crios [Coltene/Whaledent], Cerasmart [GC Europe], Shofu Block HC [Shofu], and Lava Ultimate [3M]); (2) air abrasion vs. no air abrasion; and (3) pretreatment using a silane primer (Clearfil Ceramic Primer, Kuraray) vs. a resin primer (One Coat 7 Universal, Coltene/Whaledent). Subsequently, luting composite (DuoCem, Coltene/Whaledent) was polymerized onto the substrate surface using a mold. For each combination of the levels of the three treatment factors (4 (materials) × 2 (air abrasion vs. no air abrasion; resin) × 2 (primer vs. silane primer)), n = 15, specimens were prepared. After 24 h of water storage at 37 °C and 5000 thermo-cycles (5/55 °C), TBS was measured and failure types were examined. The resulting data was analyzed using Kaplan-Meier estimates of the cumulative failure distribution function with Breslow-Gehan tests and non-parametric ANOVA (Kruskal-Wallis test) followed by the multiple pairwise Mann-Whitney U test with α-error adjustment using the Benjamini-Hochberg procedure and chi-square test (p < 0.05). RESULTS: The additional air abrasion step increased TBS values and lowered failure rates. Specimens pretreated using a resin primer showed significantly higher TBS and lower failure rates than those pretreated using a silane primer. The highest failure rates were observed for groups pretreated with a silane primer. Within the Shofu Block HC group, all specimens without air abrasion and pretreatment with a silane primer debonded during the aging procedure. CONCLUSIONS: Before fixation of CAD/CAM resin composites, the restorations should be air abraded and pretreated using a resin primer containing methyl-methacrylate to successfully bond to the luting composite. The pretreatment of the CAD/CAM resin composite using merely a silane primer results in deficient adhesion. CLINICAL RELEVANCE: For a reliable bond of CAD/CAM resin composites to the luting composite, air abrasion and a special pretreatment strategy are necessary in order to achieve promising long-term results.

Fracture resistance and 2-body wear of 3-dimensional-printed occlusal devices.

STATEMENT OF PROBLEM: Polymeric material for 3-dimensional printing can be used to fabricate occlusal devices. However, information about fracture resistance and wear is scarce. PURPOSE: The purpose of this in vitro study was to investigate the fracture resistance and 2-body wear of 3-dimensional-printed (3DP) (FotoDent splint; Dreve Dentamid GmbH), milled polymethylmethacrylate (CAM) (Temp Basic; Transpa 95H16, Zirkonzahn GmbH), and conventionally fabricated polymethylmethacrylate (CAST) (Castdon; Dreve Dentamid GmbH) occlusal devices. MATERIAL AND METHODS: A total of 96 occlusal devices were prepared according to the 3 different manufacturing techniques 3DP, CAM, and CAST (n=32). For each manufacturing technique, specimens were further divided into initial fracture resistance tests (n=16) and artificial aging in the mastication simulator (50 N, 37°C) with 2-body wear followed by fracture resistance tests (n=16). The fracture resistance was determined using a universal testing machine (1 mm/min). The wear was measured after 20 000 and 120 000 mastication cycles with the replica technique, mapped with a laser scanner, and quantified in R software. Data were analyzed using a 2-way ANOVA followed by a 1-way ANOVA with Scheffé or Games-Howell post hoc tests, repeated measures ANOVA with corrected Greenhouse-Geisser P values, and the Levene, Mann-Whitney, and paired t tests (α=.05). RESULTS: CAM presented higher initial fracture resistance than 3DP or CAST (P<.001). After mastication simulation, CAM followed by 3DP showed higher fracture resistance than CAST (P<.001). Mastication simulation decreased the fracture resistance for CAM and CAST (P<.001) but not for 3DP (P=.78). Three-dimensional-printed occlusal devices showed the highest material volume loss, followed by CAM and the lowest in CAST (P<.001). CONCLUSIONS: Three-dimensional-printed occlusal devices showed lower wear resistance and lower fracture resistance than those milled or conventionally fabricated. Therefore, only short-term application in the mouth is recommended. Further developments of occlusal device material for 3-dimensional printing are necessary.

Analysis of Drug-Drug Interactions in Swiss Claims Data Using Tizanidine and Ciprofloxacin as a Prototypical Contraindicated Combination.

BACKGROUND: Potential drug-drug interactions (pDDIs) are described in various case reports, but few studies have evaluated the impact of specific combinations on a population level. OBJECTIVE: To analyze the type and frequency of multiple contraindicated (X-pDDIs) and major interactions (D-pDDIs) and to subsequently assess the impact of the particular combination of tizanidine and ciprofloxacin on outpatient physician visits and hospitalizations. METHODS: Anonymized Swiss claims data from 524 797 patients in 2014-2015 were analyzed. First, frequencies of X- and D-pDDIs were calculated. Next, a retrospective cohort study was conducted among patients prescribed tizanidine and ciprofloxacin (exposed, n = 199) or tizanidine and other antibiotics (unexposed, n = 960). Hospitalizations and outpatient physician visits within 7, 14, and 30 days after initiation of antibiotic therapy were evaluated using multiple binary logistic regression and multiple linear regression. RESULTS: The relative frequencies of X- and D-pDDIs were 0.4% and 6.65%, respectively. In the cohort study, significant associations between exposure to tizanidine and ciprofloxacin and outpatient physician visits were identified for 14 and 30 days (odds ratio [OR] = 1.61 [95% CI = 1.17-2.24], P = 0.004, and OR = 1.59 [95% CI = 1.1-2.34], P = 0.016). A trend for increased risk of hospitalization was found for all evaluated time periods (OR = 1.68 [95% CI = 0.84-3.17], OR = 1.52 [95% CI = 0.63-3.33], and OR = 2.19 [95% CI = 0.88-5.02]). Conclusion and Relevance: The interaction between tizanidine and ciprofloxacin is not only relevant for individual patients, but also at the population level. Further investigation of the impact of other clinically relevant DDIs is necessary to improve patient safety and reduce avoidable health care utilization.

Bonding of composite resins to PEEK: the influence of adhesive systems and air-abrasion parameters.

OBJECTIVE: The objective of the study was to investigate the tensile bond strength (TBS) to polyaryletheretherketone (PEEK) after different pretreatment and conditioning methods. METHODS: Four hundred PEEK specimens were fabricated and allocated to the following air-abrasion methods (n 1 = 80/pretreatment): (i) 50 µm Al2O3 (0.05 MPa); (ii) 50 µm Al2O3 (0.35 MPa); (iii) 110 µm Al2O3 (0.05 MPa); (iv) 110 µm Al2O3 (0.35 MPa); and (v) Rocatec 110 µm (0.28 MPa). These pretreatments were combined with the following conditioning methods (n 2 = 20/pretreatment/conditioning): (a) visio.link (VL); (b) Monobond Plus/Heliobond (MH); (c) Scotchbond Universal (SU); and (d) dialog bonding fluid (DB). After veneering of all specimens with dialog occlusal and aging (28 days H2O, 37 °C + 20,000 thermal cycles, 5/55 °C), TBS was measured. Data was analysed using Kaplan-Meier survival analysis with Breslow-Gehan test and Cox-regressions. RESULTS: The major impact on TBS showed the conditioning, followed by the air-abrasion-pressure, while the grain size of the air-abrasion powder did not show any effect. Specimens air-abraded at 0.35 MPa showed the highest survival rates. However, within VL groups, this observation was not statistically significant. Within MH groups, pretreatment using 110 µm Al2O3 and 0.05 MPa resulted in higher survival rates compared to groups treated with 50 and 110 µm Al2O3 using a pressure of 0.35 MPa. The use of VL showed the highest survival rates between the adhesive systems and the TBS values higher than 25 MPa independent of the pretreatment method. As an exception, only VL showed significantly higher survival rates when compared to MH. CONCLUSIONS: The adequate choice of the adhesive system and higher pressures improved the TBS between PEEK and veneering resin composite. The particle size had no major impact. CLINICAL RELEVANCE: According to this study, best veneering of PEEK with dialog occlusal can be achieved by conditioning with visio.link in combination with the pretreatment of airborne particle abrasion at a pressure of 0.35 MPa.

Macro- and microtopographical examination and quantification of CAD-CAM composite resin 2- and 3-body wear.

STATEMENT OF PROBLEM: The selection of an appropriate restorative material based on wear behavior is important for the long-term success of a dental restoration. For computer-aided design and computer-aided manufacturing (CAD-CAM) composite resins, information about their wear resistance and wear mechanism is scarce. PURPOSE: The purpose of this in vitro study was to compare the 2- and 3-body wear of CAD-CAM composite resins with that of lithium disilicate ceramic and to develop analysis software. MATERIAL AND METHODS: Flat specimens were prepared from the following CAD-CAM composite resins: Cerasmart (CS), SHOFU Block HC (SH), Katana Avencia (KA), Brilliant Crios (BC), an experimental composite resin (EXP), and lithium disilicate ceramic IPS e.max CAD (REF). The specimens underwent 2-body wear (50 N, 5/55°C, 400 000 cycles) opposed by human enamel antagonists. Specimen wheels were prepared with each material on each wheel for 3-body wear with a millet slurry (15 N, 15% slip, 200 000 cycles). All specimens were digitized by using a dedicated laser scanner. Analysis software was developed to calculate macrotopographical examination of volume loss. The microtopography of the surfaces was examined by using scanning electron microscopy. For data analysis, the Kruskal-Wallis test with the Tukey-Kramer post hoc test and the 1-sample Wilcoxon test were used (α=.05). RESULTS: After 2-body wear simulation, SH and KA presented higher volume loss than the other CAD-CAM materials. For 3-body wear, REF had lower volume loss than CS, SH, or BC. In addition, BC led to higher volume loss than EXP. The patterns of 2- and 3-body wear were different. CONCLUSIONS: The ceramic showed good global wear resistance. The volume loss of the CAD-CAM composite resins differed and depended on the material. The 2- and 3-body wear test methods tended to differ with regard to volume loss. Examination of the worn surfaces revealed different mechanisms acting in 2- and 3-body wear test.

Computed tomographic-lymphography as a complementary technique for lymph node staging in dogs with malignant tumors of various sites.

Locoregional lymph nodes are routinely examined in order to define the spatial extent of neoplastic disease. As draining patterns of certain tumor types can be divergent from expected anatomical distribution, it is critical to sample the lymph nodes truly representing the draining area. The aim of this bicenter prospective pilot study was to describe the technique of computed tomographic (CT)-lymphography for primary draining lymph node mapping in tumor staging in dogs. Forty-five dogs with macro- or microscopic tumors in specified localizations were evaluated. Depending on body weight, 0.8-2 ml contrast agent (iohexol) was injected into four quadrants around the tumor, and CT-images were obtained at 1, 3, 6, 9, and 12 minutes post-injection. Attenuation of chosen regions of interest (Hounsfield units (HU)) and patterns of enhancement were assessed for 284 lymph nodes in the precontrast study with median HUs of 31.1 (Interquartile range (IQR) = 18.4) and for 275 in the intravenous postcontrast study with 104.3 HU (IQR = 31.2) (paired Wilcoxon test, P < 0.001). In the CT-lymphography study, 45 primary draining lymph nodes with a significantly higher median HU value of 348.5 (IQR = 591.4) (one-sample t-test, P < 0.001) were identified. Primary draining lymph nodes were found to be clearly visible after 1-3 minutes after local injection, often concurrent with a good visibility of the lymphatic vessel system. The herein described technique of peritumorally injected CT-contrast agent followed by subsequent CT-lymphography for primary draining lymph node mapping works well in a majority of cases in all investigated sites and warrants further validation for different tumor entities.

Retention Load of Telescopic Crowns with Different Taper Angles between Cobalt-Chromium and Polyetheretherketone Made with Three Different Manufacturing Processes Examined by Pull-Off Test.

PURPOSE: To investigate the retention loads of differently fabricated secondary telescopic polyetheretherketone (PEEK) crowns on cobalt-chromium primary crowns with different tapers. MATERIALS AND METHODS: Cobalt-chromium primary crowns with 0°, 1°, and 2° tapers were constructed, milled, and sintered. Corresponding secondary crowns were fabricated by milling, pressing from pellets, and pressing from granules. For these nine test groups, the pull-off tests of each crown combination were performed 20 times, and the retention loads were measured (Zwick 1445, 50 mm/min). Data were analyzed using linear regression, covariance analysis, mixed models, Kruskal-Wallis, and Mann-Whitney U-test, together with the Benferroni-Holm correction. RESULTS: The mixed models covariance analysis reinforced stable retention load values (p = 0.162) for each single test sequence. There was no interaction between the groups and the separation cycles (p = 0.179). Milled secondary crowns with 0° showed the lowest mean retention load values compared to all tested groups (p = 0.003) followed by those pressed form pellets with 1°. Regarding the different tapers, no effect of manufacturing method on the results was observed within 1° and 2° groups (p = 0.540; p = 0.052); however, among the 0° groups, the milled ones showed significantly the lowest retention load values (p = 0.002). Among the manufacturing methods, both pressed groups showed no impact of taper on the retention load values (p > 0.324 and p > 0.123, respectively), whereas among the milled secondary crowns, the 0° taper showed significantly lower retention load values than the 1° and 2° taper (p < 0.002). CONCLUSION: Based on these results, telescopic crowns made of PEEK seem to show stable retention load values for each test sequence; however, data with thermo-mechanical aging are still required. In addition, further developments in CAD/CAM manufacturing of PEEK materials for telescopic crowns are warranted, especially for 0°.

Retrospective clinical study on outcome in cats with nasal planum squamous cell carcinoma treated with an accelerated radiation protocol.

BACKGROUND: Cutaneous squamous cell carcinoma of the nasal planum in cats is a common indication for antitumor treatment such as external beam radiation therapy. Curative-intent radiation therapy has been described as a valuable treatment option, resulting in long and stable tumor control in these patients. The aim of the current study was to evaluate outcome and toxicity, as well as possible prognostic factors using an accelerated hypofractionated radiation therapy protocol. Cats with squamous cell carcinoma of the nasal planum treated with an accelerated radiation protocol (10 × 4.8 Gy, over one week) were retrospectively evaluated. Tumor- and treatment-associated variables were evaluated in respect to local control and survival. RESULTS: Forty-four cats met the inclusion criteria for this study. All cats showed complete response to therapy. Median disease-free interval (DFI) for all cases was 916 days (95% CI: 456-1377). One- and two-year DFIs were 71% (95% CI: 56-86%) and 60% (95% CI: 43-77%). Of the tested variables, only tumor volume showed a tendency to influence DFI, with larger tumors having a 5.4 times greater risk of recurrence than the smaller ones (HR 1.33 (95% CI: 0.99-1.79), p = 0.054). Median overall survival (OS) was 902 days (95% CI: 862-942). One- and 2-year OSs were 79.3% (95% CI: 67.3-91.3) and 58.4% (95% CI: 42.8-74). Of the tested variables, again, only tumor volume influenced OS with larger tumors having a 6.3 times greater risk of dying than the smaller ones (HR 1.36 (95% CI: 1.07-1.73), p = 0.010). The acute and late toxicity profile was low and hence clinically acceptable. CONCLUSIONS: Curative-intent radiation therapy with an accelerated fractionation schedule can be considered a safe, cosmetically superior treatment option for cutaneous squamous cell carcinomas of the nasal planum in cats, resulting in long and stable tumor control.

Bonding Behaviour of Polyetherketoneketone to Methylmethacrylate- and Dimethacrylate-based Polymers.

PURPOSE: To investigate the impact of pretreatment and conditioning on bonding behavior of polyetherketoneketone (PEKK) to methylmethacrylate(MMA)- and dimethacrylate(DMA)-based polymers. MATERIALS AND METHODS: 1200 PEKK substrates (Pekkton ivory) were fabricated, air abraded (110 µm, Al2O3) and divided into 8 pretreatment groups as follows: 1. Visio.link (VL); 2. VL+ opaquer; 3. Pekk Bond (PB); 4. PB + opaquer; 5. plasma; 6. plasma + opaquer; 7. plasma + VL+ opaquer; 8. plasma + PB + opaquer. A low-density cold oxygen plasma was used to treat specimens in groups 5-8. All pretreated PEKK substrates were bonded with either MMA-based polymers (denture acrylic: "Anaxdent acryline") or DMA-based polymers (veneering composites: flowable "Anaxdent dentin flow" or packable "Anaxdent dentin paste"). On denture acrylic, the anaxgum opaquer paste was applied, and on veneering composites, the anaxblend opaquer paste. All specimens were stored in water for 24 h at 37°C, and 20 specimens of each subgroup were additionally thermocycled (5°C/55°C, 10,000x). Tensile bond strength (TBS) was measured and analyzed with the general linear model analysis, Kaplan-Meier survival estimates, and Breslow-Gehan tests. RESULTS: The combination of plasma and VL showed the highest TBS results, followed by VL and the combination of plasma and PB. The lowest TBS was observed among PEKK specimens treated with plasma and without pretreatment, followed by specimens conditioned with PB. The application of an opaquer layer increased the TBS. Bonding to PEKK with MMA-based polymers showed higher TBS results than with DMA-based polymers. Among DMA-based polymers, the flowable polymer bonded significantly better to PEKK compared to paste polymer. After thermocycling, the TBS decreased. CONCLUSION: Sufficient bonding to PEKK is possible when plasma treatment is used in combination with the tested adhesives and an opaquer layer.

Dynamic In Vivo Profiling of DNA Damage and Repair after Radiotherapy Using Canine Patients as a Model.

Time resolved data of DNA damage and repair after radiotherapy elucidates the relation between damage, repair, and cell survival. While well characterized in vitro, little is known about the time-course of DNA damage response in tumors sampled from individual patients. Kinetics of DNA damage after radiotherapy was assessed in eight dogs using repeated in vivo samples of tumor and co-irradiated normal tissue analyzed with comet assay and phosphorylated H2AX (γH2AX) immunohistochemistry. In vivo results were then compared (in silico) with a dynamic mathematical model for DNA damage formation and repair. Maximum %DNA in tail was observed at 15-60 min after irradiation, with a rapid decrease. Time-courses of γH2AX-foci paralleled these findings with a small time delay and were not influenced by covariates. The evolutionary parameter search based on %DNA in tail revealed a good fit of the DNA repair model to in vivo data for pooled sarcoma time-courses, but fits for individual sarcoma time-courses suffer from the heterogeneous nature of the in vivo data. It was possible to follow dynamics of comet tail intensity and γH2AX-foci during a course of radiation using a minimally invasive approach. DNA repair can be quantitatively investigated as time-courses of individual patients by integrating this resulting data into a dynamic mathematical model.