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.

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.

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.

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.

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.

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.

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.

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.

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.

Resin cements effect on the final color of novel monolithic CAD/CAM restorations.

BACKGROUND: This study investigated the effect of resin cement shade on the final color of computer aided design/computer aided manufacture (CAD/CAM) restorations. METHODS: Thirty CAD/CAM block specimens were fabricated (14×12×1.5 mm) by cutting blocks (Vita Mark II [VM], Vita Enamic [VE], and Lava Ultimate [LU]). Forty cement specimens were prepared (14×12×0.2 mm) using resin cement (RelyX Ultimate Tr, A1, A3O, Bl). Color measurements of CAD/CAM specimens were made without (control) and with each /shade of resin cement (test) with a spectrophotometer. Color differences (ΔE00) between the control and test groups were calculated and analyzed by 2-way ANOVA and subsequent pairwise testing. Comparisons were performed by using Tukey's multiple comparison tests (α=0.05). RESULTS: Both cement shade and interaction between cement shade CAD/CAM block type parameters were significant on color differences (P<0.05). A3O cement resulted in a clinically unacceptable color differences (ΔE00>2.25) for each tested CAD/CAM blocks. ΔE00 values of VM_A1 and VE_A1 groups were also higher than clinically unacceptable level (ΔE00>2.25). ΔE00 value of VE_Tr was lower than visually perceptible level (∆E00≤1.30). There was no statistically significant difference found between the ∆E00 values of CAD/CAM blocks in the same shade of cement groups (P>0.05). CONCLUSIONS: Tested CAD/CAM blocks were similarly affected by the cement shade and thus may have similar optical features.

From Data to Improved Decisions: Operations Research in Healthcare Delivery.

BACKGROUND: The Operations Research Interest Group (ORIG) within the Society of Medical Decision Making (SMDM) is a multidisciplinary interest group of professionals that specializes in taking an analytical approach to medical decision making and healthcare delivery. ORIG is interested in leveraging mathematical methods associated with the field of Operations Research (OR) to obtain data-driven solutions to complex healthcare problems and encourage collaborations across disciplines. This paper introduces OR for the non-expert and draws attention to opportunities where OR can be utilized to facilitate solutions to healthcare problems. METHODS: Decision making is the process of choosing between possible solutions to a problem with respect to certain metrics. OR concepts can help systematically improve decision making through efficient modeling techniques while accounting for relevant constraints. Depending on the problem, methods that are part of OR (e.g., linear programming, Markov Decision Processes) or methods that are derived from related fields (e.g., regression from statistics) can be incorporated into the solution approach. This paper highlights the characteristics of different OR methods that have been applied to healthcare decision making and provides examples of emerging research opportunities. EXAMPLES: We illustrate OR applications in healthcare using previous studies, including diagnosis and treatment of diseases, organ transplants, and patient flow decisions. Further, we provide a selection of emerging areas for utilizing OR. CONCLUSIONS: There is a timely need to inform practitioners and policy makers of the benefits of using OR techniques in solving healthcare problems. OR methods can support the development of sustainable long-term solutions across disease management, service delivery, and health policies by optimizing the performance of system elements and analyzing their interaction while considering relevant constraints.

Comparative Effectiveness of Up To Three Lines of Chemotherapy Treatment Plans for Metastatic Colorectal Cancer.

Modern chemotherapy agents transformed standard care for metastatic colorectal cancer (mCRC) but raised concerns about the financial burden of the disease. We studied comparative effectiveness of treatment plans that involve up to three lines of therapies and impact of treatment sequencing on health and cost outcomes. We employed a Markov model to represent the dynamically changing health status of mCRC patients and used Monte-Carlo simulation to evaluate various treatment plans consistent with existing guidelines. We calibrated our model by a meta-analysis of published data from an extensive list of clinical trials and measured the effectiveness of each plan in terms of cost per quality-adjusted life year. We examined the sensitivity of our model and results with respect to key parameters in two scenarios serving as base case and worst case for patients' overall and progression-free survivals. The derived efficient frontiers included seven and five treatment plans in base case and worst case, respectively. The incremental cost-effectiveness ratio (ICER) ranged between $26,260 and $152,530 when the treatment plans on the efficient frontiers were compared against the least costly efficient plan in the base case, and between $21,256 and $60,040 in the worst case. All efficient plans were expected to lead to fewer than 2.5 adverse effects and on average successive adverse effects were spaced more than 9 weeks apart from each other in the base case. Based on ICER, all efficient treatment plans exhibit at least 87% chance of being efficient. Sensitivity analyses show that the ICERs were most dependent on drug acquisition cost, distributions of progression-free and overall survivals, and health utilities. We conclude that improvements in health outcomes may come at high incremental costs and are highly dependent in the order treatments are administered.

[A Study to Determine the Norms for the Trail Making Test For the Age Range of 20-49 in Turkey]. / Iz Sürme Testi’nin 20-49 Yas Araliginda Türkiye Için Norm Belirleme Çalismasi.

OBJECTIVE: The main goal of the study is to determine the normative values of Trail Making Test (TMT) for people between 20-49 years of age; to examine the effect of age, education and sex variables over TMT scores and identify the reliability coefficient of the test. METHOD: The sample of the study consisted of 133 women and 130 men, 261 voluntary and healthy participants in total. The data of the research was collected according to 3 x 2 x 2 factorial experimental design; and the participants were distributed to experimental conditions well balanced in terms of the levels of age, education and sex. TMT A and B form, and Beck Depression Scale (BDS) were applied for the assessment. RESULTS: Seven scores were calculated determining for Turkish normative values; 3 x 2 x 2 factorial multivariate variance analysis was applied in order to identify the effect of levels of age, education and sex over TMT scores. According to the results of the analyses, it was found that main effect of education was significant, while the main effects of age and sex variables were not (p<.05). The test-retest reliability coefficients of the TMT changed between .71 and .87. CONCLUSION: This study indicated that especially the TMT B and subtest scores were affected by the education in the range of 20-49 years of age. Additionally, normative values depending on the means of TMT scores for 20-49 age group were obtained in the study; it was shown that TMT was a reliable assessment tool.

Does probe's eye subthalamic nucleus length on T2W MRI correspond with microelectrode recording in patients with deep brain stimulation for advanced Parkinson's disease?

AIM: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a well-accepted treatment for patients with advanced Parkinson's disease (PD). During surgical planning for DBS, the length of the STN is taken into account and verified during microelectrode recording (MER) intraoperatively. Here, we addressed the question to which extent the length of the STN measured with the T2 weighted MRI in the probe's eye view corresponded with the intraoperatively determined length of the STN with MER. MATERIAL AND METHODS: We included 10 consecutive Parkinson's disease patients who underwent STN DBS surgery. The length of the STN in the probe's eye view mode was calculated along the trajectory of the central MER electrode crossing the STN. RESULTS: Our analysis showed no statistical difference between the length of the STN measured with the T2 weighted probe's eye view mode and the MER (right STN length 5.8 ± 0.9 mm MRI vs. 6.3 ± 0.5 mm MER, p > 0.05; left STN length 5.6 ± 0.4 mm MRI vs 5.8 ± 1 mm MER, p > 0.05). CONCLUSION: This means that the entry and the exit of the STN can be adequately estimated using the probe's eye view preoperatively.

Conversion of local anesthesia-guided deep brain stimulation of the subthalamic nucleus to general anesthesia.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) is a widely applied procedure in the treatment of patients with advanced Parkinson disease and is generally performed under local anesthesia. Here we report our experience with the conversion to general anesthesia in two patients with advanced Parkinson disease because of fear reactions intraoperatively. CASE DESCRIPTION: Patients received general anesthesia with propofol and were implanted with electrodes at the level of STN guided by multiple-microelectrode electrophysiological recordings after obtaining informed consent. During the recordings the propofol levels were reduced. Postoperative clinical assessments showed marked improvements of motor disability with significant reductions of dopaminergic medication. CONCLUSION: Our case observations document the possibility of fear reactions intraoperatively and show the possibility of conversion to general anesthesia with a successful outcome.

Syncope associated with subthalamic nucleus deep brain stimulation in a patient with Parkinson's disease.

In advanced Parkinson's disease (PD), deep brain stimulation (DBS) may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN) DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease. Case report. Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp), the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV), she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on).

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.

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.