Response inhibition according to the stimulus and food type in exogenous obesity.

OBJECTIVES: It is still unknown under which conditions response inhibition deficits occur in obesity, and how these patterns change. Methodological and experimental limitations might be predictors. The main purpose of this study was to investigate whether or not the inhibitory control process of participants with obesity and those of a healthy weight differs according to the type of stimuli. METHOD: The study sample was comprised of 51 exogenous obese and 46 healthy weight participants. Groups completed four go/no-go blocks: neutral, object, low-calorie, and high-calorie. The order of block presentation was counterbalanced. To examine inhibitory controls, repeated measures of the last factor were applied. RESULTS: Results showed that obese and healthy weight participants' response patterns changed according to the type of stimuli. Obese participants did not have problems with neutral/standard response inhibition. The inhibitory control deficits occurred in the food stimuli blocks. Also, food type was a predictor for that response pattern. The response control declined prominently in the high-calorie food condition compared to the low-calorie food condition. Error types and reaction times changed according to the stimulus and food type. DISCUSSION: In go/no-go tasks, manipulating the stimulus type, especially the food type, seems to be critical for understanding the nature of response control. The response inhibition problem was revealed in the food stimulus and changed based on the food type. These results are thought to be important for the construction of efficient weight treatment programs.

Cost-effectiveness of nivolumab versus surveillance for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence: a US payer perspective.

AIM: To evaluate the cost-effectiveness of adjuvant nivolumab compared with surveillance for the treatment of patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection from a US healthcare payer perspective and to investigate the impact of alternative modeling approaches on the cost-effectiveness results. MATERIAL AND METHODS: A four-state, semi-Markov model consisting of disease free, local recurrence, distant recurrence, and death health states was developed to investigate the cost-effectiveness of nivolumab compared with surveillance over a 30-year time horizon. The model used data from the randomized CheckMate 274 trial (NCT02632409) and published literature to inform transitions among health states, and inputs on cost, utility, adverse event, and disease management. Scenario analyses were conducted to investigate the impact of model structure and key assumptions on the results. One-way deterministic and probabilistic sensitivity analysis were conducted to investigate the robustness of the results. RESULTS: Total expected costs were higher with nivolumab ($162,278) compared with surveillance ($63,027). Nivolumab was associated with improved survival (1.61 life-years gained compared with surveillance) and an incremental gain of 0.98 quality-adjusted life-years (QALYs). Although total treatment costs were higher for nivolumab, cost offsets were observed because of delayed or avoided recurrences and deaths experienced with nivolumab compared with observation. The incremental cost-effectiveness and cost-utility ratios were $61,462/life-year and $100,930/QALY. LIMITATIONS: At the time of analysis, CheckMate 274 had limited follow-up on disease-free survival and no overall survival data. The limited evidence necessitated assumptions on modeling survival after each type of recurrence. CONCLUSIONS: Nivolumab is estimated to be a life-extending and cost-effective option for adjuvant treatment of MIUC for patients who are at high risk of recurrence after undergoing radical resection in the United States. Using a threshold of $150,000/QALY, the cost-effectiveness conclusions remained consistent across the scenario and sensitivity analyses conducted.

Challenges, considerations, and approaches for developing a cost-effectiveness model for the adjuvant treatment of muscle-invasive urothelial carcinoma: with a spotlight on nivolumab versus placebo.

AIMS: To present alternative approaches related to both structural assumptions and data sources for the development of a decision analytic model for evaluating the cost-effectiveness of adjuvant nivolumab compared with surveillance in patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection. METHODS AND RESULTS: Alternative approaches related to both structural assumptions and data sources are presented to address challenges and data gaps, as well as discussion of strengths and limitations of each approach. Specifically, challenges and considerations related to the following are presented: (1) selection of a modeling approach (partitioned survival model or state transition model) given the available evidence, (2) choice of health state structure (three- or four-state) to model disease progression and subsequent therapy, (3) modeling of outcomes from subsequent therapy using tunnel states to account for time-dependent transition probabilities or absorbing health states with one-off costs and outcomes applied, and (4) methods for modeling health-state transitions in a setting where treatment has curative intent and available survival data are immature. CONCLUSIONS: Multiple considerations must be taken into account when developing an economic model for new, emerging oncology treatments in early lines of therapy, all of which can affect the model's overall ability to estimate (quality-adjusted) survival benefits over a lifetime horizon. This paper identifies a series of key structural and analytic considerations regarding modeling of nivolumab treatment in the adjuvant MIUC setting. Several alternative approaches with regard to structure and data have been included in a flexible cost-effectiveness model so the impact of the alternative approaches on model results can be explored. The impact of these alternative approaches on cost-effectiveness results are presented in a companion article. Our findings may also help inform the development of future models for other treatments and settings in early-stage cancer.

A technique for removal of a fractured implant abutment screw.

The aim of this technique report was to present a procedure for removal of a fractured implant abutment screw. Whatever the cause, when an abutment fracture has occurred, the fractured screw segment inside the implant must be removed. The methods used by the clinicians may include the use of an endo-explorer self-made screwdriver and the use of implant repair kit available for some implant systems. The advantage of the presented method is that it may be extended to other implant systems that do not have a special repair kit and also that the technique is simple and does not require special equipment.

The effect of different surface treatments on cement-retained implant-supported restorations.

The purpose of this study was to evaluate the effects of the various surface treatment methods on the retention of single crowns on implant abutments. The study included 50 single crowns that were cemented with adhesive resin cement onto the ITI solid abutments. The specimens were randomly divided into 5 groups, each including 10 specimens according to the following surface treatments: group C, control, abutments remained unaltered as control; group L, etching with CO(2) laser; group SB, sandblasting with 50-µm Al(2)O(3); group MS: coating with titanium nitride (TiAlN) with a radiofrequency magnetron sputtering system; and group SP, silicoating by Silano-Pen. After the surface treatment procedures were finished, the casted crowns were cemented onto the abutments, and thermocycling was applied to simulate oral environment. The uniaxial tensile force was applied to all test crowns using a universal test machine (Instron) with a crosshead speed of 0.5 mm/min. The load required to dislodge each crown was recorded in Newton. The lowest tensile bond strength values were obtained with group MS (223.26 ± 14.30 N) and significantly differ from all other groups except group C. Group SB showed highest test results (506.02 ± 18.04 N) and differs from other groups (P < .05). The test values that were obtained in group MS-group C did not show significant differences (P > .05). Sandblasting is an effective method to increase bond strength. Also, Silano-Pen and laser application is advisable for increasing the crown retention to abutments. Titanium aluminum nitride coating with magnetron sputtering technique seems to be ineffective.

Designing new drug candidates as inhibitors against wild and mutant type neuraminidases: molecular docking, molecular dynamics and binding free energy calculations.

Influenza virus is the cause of the death of millions of people with about 3-4 pandemics every hundred years in history. It also turns into a seasonal disease, bringing about approximately 5-15% of the population to be infected and 290,000-650,000 people to die every year. These numbers reveal that it is necessary to be on the alert to work towards influenza in order to protect public health. There are FDA-approved antiviral drugs such as oseltamivir and zanamivir recommended by the World Center for Disease Prevention. However, after the recent outbreaks such as bird flu and swine flu, increasing studies have shown that the flu virus has gained resistance to these drugs. So, there is an urgent need to find new drugs effective against this virus. This study aims to investigate new drug candidates targeting neuraminidase (NA) for the treatment of influenza by using computer aided drug design approaches. They involve virtual scanning, de novo design, rational design, docking, MD, MMGB/PBSA. The investigation includes H1N1, H5N1, H2N2 and H3N2 neuraminidase proteins and their mutant variants possessing resistance to FDA-approved drugs. Virtual screening consists of approximately 30 thousand molecules while de novo and rational designs produced over a hundred molecules. These approaches produced three lead molecules with binding energies for both non-mutant (-34.84, -59.99 and -60.66 kcal/mol) and mutant (-40.40, -58.93, -76.19 kcal/mol) H2N2 NA calculated by MM-PBSA compared with those of oseltamivir -25.64 and -18.40 respectively. The results offer new drug candidates against influenza infection.Communicated by Ramaswamy H. Sarma.

Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma.

Aim: Network meta-analyses (NMAs) increasingly feature time-varying hazards to account for non-proportional hazards between different drug classes. This paper outlines an algorithm for selecting clinically plausible fractional polynomial NMA models. Methods: The NMA of four immune checkpoint inhibitors (ICIs) + tyrosine kinase inhibitors (TKIs) and one TKI therapy for renal cell carcinoma (RCC) served as case study. Overall survival (OS) and progression free survival (PFS) data were reconstructed from the literature, 46 models were fitted. The algorithm entailed a-priori face validity criteria for survival and hazards, based on clinical expert input, and predictive accuracy against trial data. Selected models were compared with statistically best-fitting models. Results: Three valid PFS and two OS models were identified. All models overestimated PFS, the OS model featured crossing ICI + TKI versus TKI curves as per expert opinion. Conventionally selected models showed implausible survival. Conclusion: The selection algorithm considering face validity, predictive accuracy, and expert opinion improved the clinical plausibility of first-line RCC survival models.

Use of artificial neural network in differentiation of subgroups of temporomandibular internal derangements: a preliminary study.

PURPOSE: Artificial neural networks (ANNs) have been developed in the past few decades for many different applications in medical science and in biomedical research. The use of neural networks in oral and maxillofacial surgery is limited. The aim of this study was to determine the use of ANNs for the prediction of 2 subgroups of temporomandibular joint (TMJ) internal derangements (IDs) and normal joints using characteristic clinical signs and symptoms of the diseases. MATERIALS AND METHODS: Clinical symptoms and diagnoses of 161 patients with TMJ ID were considered the gold standard and were employed to train a neural network. After the training process, the symptoms and diagnoses of 58 new patients were used to verify the network's ability to diagnose. The diagnoses obtained from ANNs were compared with diagnoses of a surgeon experienced in temporomandibular disorders. The sensitivity and specificity of ANNs in predicting subtypes of TMJ ID were evaluated using clinical diagnosis as the gold standard. RESULTS: Eight cases evaluated as bilaterally normal in clinical examination were evaluated as normal by ANN. In detecting unilateral anterior disc displacement with reduction (ADDwR; clicking), the sensitivity and specificity of ANN were 80% and 95%, respectively. In detecting unilateral anterior disc displacement without reduction (ADDwoR; locking), the sensitivity and specificity of ANN were 69% and 91%, respectively. In detecting bilateral ADDwoR, the sensitivity and specificity of ANN were 37% and 100%, respectively. In detecting bilateral ADDwR, the sensitivity and specificity of ANN were 100% and 89%, respectively. In detecting cases of ADDwR at 1 side and ADDwoR at the other side, the sensitivity and specificity of ANN were 44% and 93%, respectively. CONCLUSION: The application of ANNs for diagnosis of subtypes of TMJ IDs may be a useful supportive diagnostic method, especially for dental practitioners. Further research, including advanced network models that use clinical data and radiographic images, is recommended.

Effect of pre-processing methods on bond strength between acrylic resin teeth and acrylic denture base resin.

OBJECTIVES: This study evaluated the effects of various pre-processing methods on the bond strength between resin and denture teeth. BACKGROUNDS: Debonding of acrylic resin teeth from denture base material is a problem for patients wearing complete dentures. MATERIALS AND METHODS: Four experimental groups (n = 30) were investigated by subjecting tooth-resin bonding to tensile loading. Specimens were prepared and tested according to the methods of the International Standards Organization (ISO 22112:2005) using a special assembly. Four pre-processing surface treatments of teeth were applied: (i) ST(1), no treatment applied (control); (ii) ST(2) , wax solvent (Dewaks, Faber Kimya & Ilaç, Turkey); (iii) ST(3), boiling water followed by conditioning with methyl methacrylate (MMA) monomer (Meliodent, Bayer Dental, Germany); (iv) ST(4), boiling water followed by wax solvent agent and finally MMA monomer application. Bond strength test was performed using a universal testing machine. RESULTS: All the strength values of the test groups were within clinically acceptable limits. The lowest values were from the ST(1) group and the highest values were in the ST(4) group. CONCLUSIONS: Wax elimination methods affected bonding strength. Application of wax solvent and MMA monomer to the ridge lap surfaces of the teeth gave the best results. In clinical practice, this application procedure may decrease the bonding failure of denture teeth.

A technique to facilitate the fabrication of provisional restorations for ITI solid abutments.

The aim of this technique report was to present a procedure for the fabrication of provisional restorations for ITI solid abutments using impression caps in the laboratory with a number of advantages over intraoral techniques. There may be no need for cementation, and elimination of cementation may assist tissue healing.

Disease-free survival as a surrogate endpoint for overall survival in adults with resectable esophageal or gastroesophageal junction cancer: A correlation meta-analysis.

OBJECTIVES: To evaluate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) using aggregate-level data from resectable esophageal or gastroesophageal junction cancer (EC/GEJC) trials assessing therapies in (neo)adjuvant and perioperative settings. METHODS: A systematic literature review was conducted to identify trials reporting OS and DFS, or compatible progression-free survival (PFS). Bivariate random-effects meta-analysis was used to estimate correlation between the treatment effects on DFS/PFS and OS, and weighted linear regression models assuming trial sample sizes as weights were used to estimate surrogacy equations. The primary analysis consisted of trials across all treatment settings, and secondary analysis consisted of trials only in the adjuvant setting. Leave-one-out cross-validation (LOOCV) was performed to measure the stability and predictive accuracy of the surrogacy equations while surrogate threshold effects (STE)-the minimum treatment effect on DFS/PFS that would translate into a positive OS benefit-were derived to measure their usefulness. RESULTS: The primary analysis included 26 trials. The estimated correlation coefficient between the hazard ratio (HR) of DFS/PFS (HRDFS/PFS) and HR of OS (HROS) was 0.83 (95% confidence interval [CI]: 0.70-0.90). The estimated surrogacy equation was log(HROS) = 0.80 × log(HRDFS/PFS) with a corresponding STE of 0.82. Reported HROS was within the 95% prediction interval of the predicted HROS from the model for more than 95% of the trials in the LOOCV, indicating a valid model. Secondary analysis included 7 trials with an estimated correlation coefficient of 0.76 (95% CI: 0.18-0.95). Through LOOCV, the surrogacy equation in the adjuvant setting was deemed valid. CONCLUSIONS: Our meta-analysis suggests that HRDFS/PFS -where DFS/PFS is defined as time from resection to disease recurrence (local, locoregional, or distant) or death-is correlated to HROS, and a valid and useful surrogate predictor for HROS in the neoadjuvant, perioperative, or adjuvant settings.

Cost-Utility of Nivolumab Plus Ipilimumab in First-Line Treatment of Advanced Melanoma in the United States: An Analysis Using Long-Term Overall Survival Data from Checkmate 067.

OBJECTIVE: The aim of this study was to evaluate the cost-utility of nivolumab plus ipilimumab (NIVO + IPI) versus other first-line therapies for advanced melanoma in the United States (US) from the third-party payer perspective. METHODS: This analysis estimated total expected life-years (LYs), quality-adjusted LYs (QALYs), and costs for first-line treatments of advanced melanoma during a 30-year time horizon using indirect treatment comparisons based on time-varying hazard ratios (HRs) and a three-state partitioned survival model. Overall survival (OS) and progression-free survival reference curves were extrapolated based on 5-year follow-up from the phase III Checkmate 067 trial (NCT01844505). Comparators of NIVO + IPI were NIVO, IPI, pembrolizumab, dabrafenib plus trametinib, encorafenib plus binimetinib (ENCO + BINI), and vemurafenib plus cobimetinib. Drug acquisition costs, treatment administration costs, follow-up time, subsequent therapy data, and adverse event frequencies were obtained from published sources. Utility weights were estimated from Checkmate 067, which compared NIVO + IPI or NIVO monotherapy with IPI monotherapy as first-line therapy in advanced melanoma. A 3% annual discount rate was applied to costs and outcomes. Sensitivity scenarios for BRAF-mutant subgroups were conducted. RESULTS: NIVO + IPI was estimated to generate the longest OS and the highest total costs versus all comparators, accruing 6.99 LYs, 5.70 QALYs, and $469,469 over the 30-year time horizon. The incremental cost utility of NIVO + IPI versus comparators ranged from $2130 per QALY (versus ENCO + BINI) to $76,169 per QALY (versus NIVO). In all base-case and most sensitivity analyses, the incremental cost-utility ratios for NIVO + IPI were below $100,000 per QALY. CONCLUSIONS: NIVO + IPI is estimated to be a life-extending and cost-effective treatment versus other therapies in the US, with base-case incremental cost-utility ratios below $100,000 per QALY.

Heterogeneity in Survival with Immune Checkpoint Inhibitors and Its Implications for Survival Extrapolations: A Case Study in Advanced Melanoma.

Background: Survival heterogeneity and limited trial follow-up present challenges for estimating lifetime benefits of oncology therapies. This study used CheckMate 067 (NCT01844505) extended follow-up data to assess the predictive accuracy of standard parametric and flexible models in estimating the long-term overall survival benefit of nivolumab plus ipilimumab (an immune checkpoint inhibitor combination) in advanced melanoma. Methods: Six sets of survival models (standard parametric, piecewise, cubic spline, mixture cure, parametric mixture, and landmark response models) were independently fitted to overall survival data for treatments in CheckMate 067 (nivolumab plus ipilimumab, nivolumab, and ipilimumab) using successive data cuts (28, 40, 52, and 60 mo). Standard parametric models allow survival extrapolation in the absence of a complex hazard. Piecewise and cubic spline models allow additional flexibility in fitting the hazard function. Mixture cure, parametric mixture, and landmark response models provide flexibility by explicitly incorporating survival heterogeneity. Sixty-month follow-up data, external ipilimumab data, and clinical expert opinion were used to evaluate model estimation accuracy. Lifetime survival projections were compared using a 5% discount rate. Results: Standard parametric, piecewise, and cubic spline models underestimated overall survival at 60 mo for the 28-mo data cut. Compared with other models, mixture cure, parametric mixture, and landmark response models provided more accurate long-term overall survival estimates versus external data, higher mean survival benefit over 20 y for the 28-mo data cut, and more consistent 20-y mean overall survival estimates across data cuts. Conclusion: This case study demonstrates that survival models explicitly incorporating survival heterogeneity showed greater accuracy for early data cuts than standard parametric models did, consistent with similar immune checkpoint inhibitor survival validation studies in advanced melanoma. Research is required to assess generalizability to other tumors and disease stages. Highlights: Given that short clinical trial follow-up periods and survival heterogeneity introduce uncertainty in the health technology assessment of oncology therapies, this study evaluated the suitability of conventional parametric survival modeling approaches as compared with more flexible models in the context of immune checkpoint inhibitors that have the potential to provide lasting survival benefits.This study used extended follow-up data from the phase III CheckMate 067 trial (NCT01844505) to assess the predictive accuracy of standard parametric models in comparison with more flexible methods for estimating the long-term survival benefit of the immune checkpoint inhibitor combination of nivolumab plus ipilimumab in advanced melanoma.Mixture cure, parametric mixture, and landmark response models provided more accurate estimates of long-term overall survival versus external data than other models tested.In this case study with immune checkpoint inhibitor therapies in advanced melanoma, extrapolation models that explicitly incorporate differences in cancer survival between observed or latent subgroups showed greater accuracy with both early and later data cuts than other approaches did.

Determination of resin bond strength to zirconia ceramic surface using different primers.

OBJECTIVE: To evaluate the effect of different primers on the bond strength of adhesive resin cement to zirconia ceramic surface in vitro. MATERIAL AND METHODS: Thirty zirconia disk-shaped ceramic specimens (10×2 mm²) were divided into three equal groups for the application of different primers: Monobond-S, Clearfil Ceramic Primer and Signum Zirconia Bond. A further 10 specimens served as a control group. Forty composite resin blocks (6×2 mm²) were cemented (Panavia F 2.0) to zirconia ceramic specimens. Shear bond strengths were measured. Treated zirconia ceramic surfaces were examined using scanning electron microscopy. RESULTS: One-way ANOVA showed that the application of different primers affected the shear bond strength of adhesive resin cement to zirconia ceramic. The highest test values were obtained with application of Signum Zirconia Bond, and the lowest values were obtained in the control group. CONCLUSION: Signum Zirconia Bond is effective for increasing the bond strength of adhesive resin cement to zirconia ceramic.

Effect of air abrasion particles on the bond strength of adhesive resin cement to zirconia core.

OBJECTIVE: To evaluate the effect of air abrasion with different particles of different sizes and forms on the shear bond strength of adhesive resin cement to zirconia core. MATERIAL AND METHODS: Sixty zirconia core disks were produced and sintered. The specimens were divided into six equal groups for application of air abrasion procedures. The surfaces of the specimens were treated with one of five air abrasion particles: 30 µm silica-coated aluminum oxide particles; 1-3 µm synthetic diamond particles; 110 µm aluminum oxide particles; 30-50 µm synthetic diamond particles; and 60-80 µm cubic boron nitride particles. The remaining 10 specimens were untreated and served as controls. Composite resin disks were cemented to each of the zirconia core specimens. All specimens were stored in distilled water at 37°C for 24 h and thermocycled for 6000 cycles. The shear bond strength was measured using a universal testing machine at a crosshead speed of 1 mm/min. Data were statistically analyzed by one-way ANOVA with Tamhane tests (α = 0.05). The effect of the air abrasion procedures was examined using scanning electron microscopy. RESULTS: Air abrasion with different materials affected the bond strength (P < 0.001). The highest bond strengths were obtained by air abrasion with 30-50 µm synthetic diamond particles; the lowest bond strengths were obtained in the control group (P < 0.001). CONCLUSION: Air abrasion with 30-50 µm synthetic diamond particles, 60-80 µm cubic boron nitride particles and 110 µm aluminum oxide particles showed higher bond strength values than other methods.

The effect of screw color and technique to fill access hole on the final color of screw-retained implant crowns.

The purpose of this study was to investigate the effect of screw color and thickness of the composite on the final implant color. Gray and golden-colored titanium specimens were used as 2 different backgrounds. Composite disks were made in different thicknesses. Titanium and composite disk samples were placed into a metal mold as in the test groups for color measurement. The background color did not affect the final color. Composite resin thickness affected the final color.

What Did Time Tell Us? A Comparison and Retrospective Validation of Different Survival Extrapolation Methods for Immuno-Oncologic Therapy in Advanced or Metastatic Renal Cell Carcinoma.

BACKGROUND: The immuno-oncologic (IO) mechanism of action may lead to an overall survival (OS) hazard that changes over time, producing shapes that standard parametric extrapolation methods may struggle to reflect. Furthermore, selection of the most appropriate extrapolation method for health technology assessment is often based on trial data with limited follow-up. OBJECTIVE: To examine this problem, we fitted a range of extrapolation methods to patient-level survival data from CheckMate 025 (NCT01668784, CM-025), a phase III trial comparing nivolumab with everolimus for previously treated advanced renal cell carcinoma (aRCC), to assess their predictive accuracy over time. METHODS: Six extrapolation methods were examined: standard parametric models, natural cubic splines, piecewise models combining Kaplan-Meier data with an exponential or non-exponential distribution, response-based landmark models, and parametric mixture models. We produced three database locks (DBLs) at minimum follow-ups of 15, 27, and 39 months to align with previously published CM-025 data. A three-step evaluation process was adopted: (1) selection of the distribution family for each method in each of the three DBLs, (2) internal validation comparing extrapolation-based landmark and mean survival with the latest CM-025 dataset (minimum follow-up, 64 months), and (3) external validation of survival projections using clinical expert opinion and long-term follow-up data from other nivolumab studies in aRCC (CheckMate 003 and CheckMate 010). RESULTS: All extrapolation methods, with the exception of mixture models, underestimated landmark and mean OS for nivolumab compared with CM-025 long-term follow-up data. OS estimates for everolimus tended to be more accurate, with four of the six methods providing landmark OS estimates within the 95% confidence interval of observed OS as per the latest dataset. The predictive accuracy of survival extrapolation methods fitted to nivolumab also showed greater variation than for everolimus. The proportional hazards assumption held for all DBLs, and a dependent log-logistic model provided reliable estimates of longer-term survival for both nivolumab and everolimus across the DBLs. Although mixture models and response-based landmark models provided reasonable estimates of OS based on the 39-month DBL, this was not the case for the two earlier DBLs. The piecewise exponential models consistently underestimated OS for both nivolumab and everolimus at clinically meaningful pre-specified landmark time points. CONCLUSIONS: This aRCC case study identified marked differences in the predictive accuracy of survival extrapolation methods for nivolumab but less so for everolimus. The dependent log-logistic model did not suffer from overfitting to early DBLs to the same extent as more complex methods. Methods that provide more degrees of freedom may accurately represent survival for IO therapy, particularly if data are more mature or external data are available to inform the long-term extrapolations.

The effect of laser treatment on bonding between zirconia ceramic surface and resin cement.

OBJECTIVE: The purpose of this in-vitro study was to evaluate and compare the effects of different surface treatments and laser irradiation on the shear bond strength of resin cement to zirconia-based ceramic. MATERIAL AND METHODS: Forty zirconia core specimens (10-mm diameter, 2-mm thickness) were produced and embedded in the centers of autopolymerizing acrylic resin blocks. Subsequently, specimens were randomly divided into four groups, each containing 10 specimens, for different surface treatment methods. The details of the groups are as follows: Group C, no treatment applied (control); Group SB, bonding surfaces of ceramic disks were airborne particle-abraded with 110-µm alumina oxide particles; Group HF, bonding surfaces of ceramic disks were etched with 9.6% hydrofluoric acid; and Group L, bonding surfaces of ceramic disks were irradiated by a CO2 laser. A total of 40 composite resin disks were fabricated and cemented with an adhesive resin cement to the specimen surfaces. A universal test machine was used for the shear bond strength test at a crosshead speed of 1 mm/min. RESULTS: The highest shear bond strength values were obtained with Group L (20.99 ± 3.77 MPa) and the lowest values with Group C (13.39 ± 3.10 MPa). Although there was no significant difference between Groups C, HF and SB (P > 0.05), Group L showed a significant difference from all other groups (p < 0.05). CONCLUSION: All surface treatment methods improved the bond strength between resin cement and the zirconium oxide ceramic surface. CO2 laser etching may represent an effective method for conditioning zirconia surfaces, enhancing micromechanical retention and improving the bond strength of resin cement on zirconia ceramic.

Could Microwave Glazing Be Considered as an Alternative to Conventional Surface Finishing Methods of Ceramic Materials in Terms of Color Stability?

PURPOSE: To examine microwave heating for the purpose of ceramic glazing as an alternative to conventional methods in terms of color stability. MATERIALS AND METHODS: Thirty disk-shaped specimens (11 × 2 mm) of VITA VM 9, VITA VM 13, VITA VMK 95, and IPS e.max Ceram veneers were prepared (n = 30 each). The specimens were further divided into three subgroups according to surface finishing procedure (polishing, conventional oven glazing, or microwave glazing [n = 10 each]). The related surface finishing procedure was applied according to the manufacturers' instructions. Color differences (ΔE) of the ceramic samples stored in a coffee solution at 37°C for 168 hours were determined using spectrophotometry. Data were analyzed using two-way ANOVA. The group differences were analyzed using Tukey HSD test. RESULTS: Microwave-glazed specimens showed similar ΔE values to conventionally glazed specimens for the tested ceramics (P > .05). Polished specimens showed higher ΔE values than glazed specimens for the investigated ceramic materials, and the difference was significant for VITA VMK 95 and Vita VM9 (P ≤ .05). CONCLUSION: Microwave glazing has the advantage of decreasing glazing time to a few minutes and could be considered as an alternative method to conventional oven glazing and polishing with respect to color stability.

Optimizing the start time of statin therapy for patients with diabetes.

BACKGROUND: Clinicians often use validated risk models to guide treatment decisions for cardiovascular risk reduction. The most common risk models for predicting cardiovascular risk are the UKPDS, Framingham, and Archimedes models. In this article, the authors propose a model to optimize the selection of patients for statin therapy of hypercholesterolemia, for patients with type 2 diabetes, using each of the risk models. For each model,they evaluate the role of age, gender, and metabolic state on the optimal start time for statins. METHOD: Using clinical data from the Mayo Clinic electronic medical record, the authors construct a Markov decision process model with health states composed of cardiovascular events and metabolic factors such as total cholesterol and high-density lipoproteins. They use it to evaluate the optimal start time of statin treatment for different combinations of cardiovascular risk models and patient attributes. RESULTS: The authors find that treatment decisions depend on the cardiovascular risk model used and the age, gender, and metabolic state of the patient. Using the UKPDS risk model to estimate the probability of coronary heart disease and stroke events, they find that all white male patients should eventually start statin therapy; however, using Framingham and Archimedes models in place of UKPDS, they find that for male patients at lower risk, it is never optimal to initiate statins. For white female patients, the authors also find some patients for whom it is never optimal to initiate statins. Assuming that age 40 is the earliest possible start time, the authors find that the earliest optimal start times for UKPDS, Framingham, and Archimedes are 50, 46, and 40, respectively, for women. For men, the earliest optimal start times are 40, 40, and 40, respectively. CONCLUSIONS: In addition to age, gender, and metabolic state, the choice of cardiovascular risk model influences the apparent optimal time for starting statins in patients with diabetes.