Wear of two artificial tooth materials in vivo: a 12-month pilot study.

STATEMENT OF PROBLEM: Wear of methacrylate artificial teeth resulting in vertical loss is a problem for both dentists and patients. PURPOSE: The purpose of this study was to quantify wear of artificial teeth in vivo and to relate it to subject and tooth variables. MATERIAL AND METHODS: Twenty-eight subjects treated with complete dentures received 2 artificial tooth materials (polymethyl methacrylate (PMMA)/double-cross linked PMMA fillers; 35%/59% (SR Antaris DCL, SR Postaris DCL); experimental 48%/46%). At baseline and after 12 months, impressions of the dentures were poured with improved stone. After laser scanning, the casts were superimposed and matched. Maximal vertical loss (mm) and volumetric loss (mm(3)) were calculated for each tooth and log-transformed to reduce variability. Volumetric loss was related to the occlusally active surface area. Linear mixed models were used to study the influence of the factors jaw, tooth, and material on adjusted (residual) wear values (alpha=.05). RESULTS: Due to drop outs (n=5) and unmatchable casts (n=3), 69% of all teeth were analyzed. Volumetric loss had a strong linear relationship to surface area (P<.001); this was less pronounced for vertical loss (P=.004). The factor showing the highest influence was the subject. Wear was tooth dependent (increasing from incisors to molars). However, these differences diminished once the wear rates were adjusted for occlusal area, and only a few remained significant (anterior versus posterior maxillary teeth). Another influencing factor was the age of the subject. CONCLUSIONS: Clinical wear of artificial teeth is higher than previously measured or expected. The presented method of analyzing wear of artificial teeth using a laser-scanning device seemed suitable.

What is "clinical data"? Why and how can they be collected during field surveys on medicinal plants?

ETHNOPHARMACOLOGICAL RELEVANCE: "Reverse pharmacology", also called "bedside-to-bench" or "field to pharmacy" approach, is a research process starting with documentation of clinical outcome as observed by patients with different therapeutic regimens. The treatment most significantly associated with cure is selected for future studies: first, clinical safety and efficacy; then in vivo and vitro studies. Some clinical data, i.e. details on patient status and progress, can be collected during ethnobotanical surveys; they will help clinical researchers and, once effectiveness and safety are established, will also help users of traditional medicine make safer and more effective choices. To gather clinical data successfully, ethnopharmacologists need to be backed by an appropriate team of specialists in medicine and epidemiology. Ethnopharmacologists can also gather important data on traditional medicine safety. MATERIALS AND METHODS: The first step is to create a consensus on the meaning of "clinical data", their interest and importance. An understanding of why "a cure is not a proof of effectiveness" is a starting point to avoid faulty interpretation of the clinical observations. RESULTS: Experience showed that, with the "bedside-to-bench" approach, a treatment derived from traditional recipe can be scientifically validated (in terms of safety and effectiveness) with a cost of less than a million euros, thus providing an end-product that is affordable, available and sustainable. CONCLUSIONS: With rigorous clinical study results, medicinal plant users gain the possibility to refine heath strategies. The field surveyor may gain a better relationship with the population, once she/he is seen as bringing information useful for the quality of care in the community.

Need of reduced and harmonized bureaucracy in multi-centre clinical research - a case-report from a Swiss trial

Introduction: We launched an investigator-initiated study (ISRCTN31181395) to evaluate the potential benefit of pharmacokinetic-guided dosage individualization of imatinib for leukaemiapatients followed in public and private sectors. Following approval by the research ethics committee (REC) of the coordinating centre, recruitment throughout Switzerland necessitatedto submit the protocol to 11 cantonal RECs.Materials and Methods: We analysed requirements and evaluation procedures of the 12 RECs with associated costs.Results: 1-18 copies of the dossier, in total 4300 printed pages, were required (printing/posting costs: ~300 CHF) to meet initial requirements. Meeting frequencies of RECs ranged between 2 weeks and 2 months, time from submission to fi rst feedback took 2-75 days. Study approval was obtained from a chairman, a subor the full committee, the evaluation work being invoiced by0-1000 CHF (median: 750 CHF, total: 9200 CHF). While 5 RECs gave immediate approval, the other 6 rose in total 38 queries before study release, mainly related to wording in the patient information, leading to 7 different fi nal versions approved. Submission tasks employed an investigator half-time over about 6 months.Conclusion: While the necessity of clinical research evaluation by independent RECs is undisputed, there is a need of further harmonization and cooperation in evaluation procedures. Current administrative burden is indeed complex, time-consuming and costly. A harmonized electronic application form, preferably compatible with other regulatory bodies and European countries, could increase transparency, improve communication, and encourage academic multi-centre clinical research in Switzerland.

Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial.

PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.

Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features.

BACKGROUND: Differences exist between the proximal and distal colon in terms of developmental origin, exposure to patterning genes, environmental mutagens, and gut flora. Little is known on how these differences may affect mechanisms of tumorigenesis, side-specific therapy response or prognosis. We explored systematic differences in pathway activation and their clinical implications. MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis. A subset of 1404 samples had molecular data, including gene expression and DNA copy number profiles for 589 and 199 samples, respectively. In addition, 413 colon adenocarcinoma from TCGA collection were also analyzed. Tumor side-effect on anti-epidermal growth factor receptor (EGFR) therapy was assessed in a cohort of 325 metastatic patients. Outcome variables considered were relapse-free survival and survival after relapse (SAR). RESULTS: Proximal carcinomas were more often mucinous, microsatellite instable (MSI)-high, mutated in key tumorigenic pathways, expressed a B-Raf proto-oncogene, serine/threonine kinase (BRAF)-like and a serrated pathway signature, regardless of histological type. Distal carcinomas were more often chromosome instable and EGFR or human epidermal growth factor receptor 2 (HER2) amplified, and more frequently overexpressed epiregulin. While risk of relapse was not different per side, SAR was much poorer for proximal than for distal stage III carcinomas in a multivariable model including BRAF mutation status [N = 285; HR 1.95, 95% CI (1.6-2.4), P < 0.001]. Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy, in line with the predictions of our pathway enrichment analysis. CONCLUSIONS: Colorectal carcinoma side is associated with differences in key molecular features, some immediately druggable, with important prognostic effects which are maintained in metastatic lesions. Although within side significant molecular heterogeneity remains, our findings justify stratification of patients by side for retrospective and prospective analyses of drug efficacy and prognosis.

Patient- and therapy-related factors on the wear of denture teeth : results of a clinical trial

OBJECTIVE: When we examined a previously published prospective multi-center clinical trial in which complete denture-wearers were followed over a period of 2 years, we found that about 30% of the variability in the clinical wear data of denture teeth was due to unknown characteristics of the subjects. In the second part of the study, we try to identify which patient- and therapy-related factors may explain some of this variability. METHODS: The clinical wear data of denture teeth at different recall times (6, 12, 18, 24 months) in 89 subjects (at baseline) were correlated with the following parameters, which may all have an influence on the wear of denture teeth: age, gender, bruxism as reported by the subjects, number of prostheses used so far, time since last extraction, smoking, fit of dentures as judged by the subject and the clinician, average denture wearing time and wearing of denture during the night. To evaluate the influence of the different patient- and therapy-related variables, both a univariate analysis (one extra factor to the model) and a multivariate analysis were carried out using linear mixed models with the variable Log mean as the outcome. RESULTS: None of the patient- and therapy-related parameters showed a statistically significant effect on the wear of denture teeth. There was, however, a trend for women to show less wear compared to men and a trend of decreasing wear with increasing age. SIGNIFICANCE: Further research is required to identify the factors which are responsible for the high variability observed between the subjects regarding clinical wear data.

Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: Results from the randomized controlled I-COME Trial

Introduction: Imatinib trough plasma concentrations (Cmin) have been correlated with treatment response in chronic myeloid leukemia (CML) patients. The use of Cmin monitoring for optimizing imatinib dosage (therapeutic drug monitoring [TDM]) is therefore proposed for patients with unsatisfying response or tolerance ("rescue TDM"). A cycle of "routine TDM" for dosage individualization could also be beneficial to prevent unfavorable events, yet its clinical usefulness has not been evaluated. We aimed to assess prospectively whether a "routine TDM" intervention targeting imatinib Cmin of 1000 ng/mL (tolerance, 750-1500 ng/mL) could improve efficacy, tolerance, and persistence on treatment compared with "rescue TDM" use only. Patients (or Materials) and Methods: The Swiss Imatinib COncentration Monitoring Evaluation (I-COME) study was a multicenter randomized controlled trial (ISRCTN31181395). Adult patients in chronic or accelerated phase CML receiving imatinib ≤5 years were eligible. Patients were randomly (1:1) allocated to receive "routine TDM" intervention or to serve as controls with access only to "rescue TDM". All had 1-year follow-up. The primary endpoint was a combined efficacy-safety outcome (failure- and toxicity-free survival without imatinib discontinuation), analyzed in intention-to-treat. Results: Among 56 CML recruited patients, 55 had their molecular and cytogenetic response measured. 14/27 of patients receiving "routine TDM" (52% [33%-71%]) remained event-free versus 16/28 of control patients with "rescue TDM" only (57% [39%-75%]; P=0.69). In the "routine TDM" group, dosage recommendations were adopted entirely in 50% of patients (median Cmin at study end, 895 ng/mL; CV = 33%). These patients had fewer unfavorable events (28% [5%-52%]) compared with patients not receiving the advised dosage (77% [54%-99%]; P = 0.03; median Cmin at study end, 648 ng/mL; CV = 38%). Conclusion: This first prospective target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" of imatinib, especially due to a small patient number and limited prescriber's adherence to dosage recommendations. Nevertheless, the patients receiving the advised dosage more often met target concentrations and the combined outcome (efficacy, tolerance, and persistence). A cycle of routine TDM could thus be favorable, at least in patients eligible for dosage adjustment. Its usefulness should, however, be further confirmed in larger trials.

Orthopedic implant used as drug delivery system: clinical situation and state of the research.

A partial review is proposed on the existing literature for the research performed in orthopedic implant used as drug delivery system. In the first part, an evaluation is given on the clinical need to deliver a drug in the surrounding of an implant. Secondly, a review of the clinical situation is developed for implants already used as drug delivery system. Experimental works performed for local delivery are reported. In particular, a description is given on the in vitro and in vivo studies where the implant is coated with different proteins or drugs. Finally, a conclusion is proposed on the next step in the development of orthopedic implant as drug delivery system mentioning also the industrial situation.

Clinical review--breast adenoid cystic carcinoma.

OBJECTIVES: To review the published literature on the diagnosis and management of adenoid cystic carcinoma (ACC) of the breast.¦MATERIALS AND METHODS: Papers were identified by searching PubMed using the terms « adenoid cystic carcinoma » and « breast ». Additional papers were identified by reviewing references of relevant articles.¦RESULTS: ACC of the breast is a rare tumour comprising less than 0.1% of breast malignancies. Its cellular origin in the breast remains unclear. The histological characteristics of ACC in the breast are similar to those of ACC of the salivary glands. However the prognosis of ACC of the breast is better than that of other localizations with prolonged survival. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients.¦CONCLUSIONS: ACC of the breast has a favourable prognosis. An accurate diagnosis and appropriate treatment are therefore important.

Round robin test: wear of nine dental restorative materials in six different wear simulators - supplement to the round robin test of 2005.

OBJECTIVE: The purpose of the present study was to submit the same materials that were tested in the round robin wear test of 2002/2003 to the Alabama wear method. METHODS: Nine restorative materials, seven composites (belleGlass, Chromasit, Estenia, Heliomolar, SureFil, Targis, Tetric Ceram) an amalgam (Amalcap) and a ceramic (IPS Empress) have been submitted to the Alabama wear method for localized and generalized wear. The test centre did not know which brand they were testing. Both volumetric and vertical loss had been determined with an optical sensor. After completion of the wear test, the raw data were sent to IVOCLAR for further analysis. The statistical analysis of the data included logarithmic transformation of the data, the calculation of relative ranks of each material within each test centre, measures of agreement between methods, the discrimination power and coefficient of variation of each method as well as measures of the consistency and global performance for each material. RESULTS: Relative ranks of the materials varied tremendously between the test centres. When all materials were taken into account and the test methods compared with each other, only ACTA agreed reasonably well with two other methods, i.e. OHSU and ZURICH. On the other hand, MUNICH did not agree with the other methods at all. The ZURICH method showed the lowest discrimination power, ACTA, IVOCLAR and ALABAMA localized the highest. Material-wise, the best global performance was achieved by the leucite reinforced ceramic material Empress, which was clearly ahead of belleGlass, SureFil and Estenia. In contrast, Heliomolar, Tetric Ceram and especially Chromasit demonstrated a poor global performance. The best consistency was achieved by SureFil, Tetric Ceram and Chromasit, whereas the consistency of Amalcap and Heliomolar was poor. When comparing the laboratory data with clinical data, a significant agreement was found for the IVOCLAR and ALABAMA generalized wear method. SIGNIFICANCE: As the different wear simulator settings measure different wear mechanisms, it seems reasonable to combine at least two different wear settings to assess the wear resistance of a new material.

Osteoporotic fracture risk in elderly women: estimation with quantitative heel US and clinical risk factors

PURPOSE: To derive a prediction rule by using prospectively obtained clinical and bone ultrasonographic (US) data to identify elderly women at risk for osteoporotic fractures. MATERIALS AND METHODS: The study was approved by the Swiss Ethics Committee. A prediction rule was computed by using data from a 3-year prospective multicenter study to assess the predictive value of heel-bone quantitative US in 6174 Swiss women aged 70-85 years. A quantitative US device to calculate the stiffness index at the heel was used. Baseline characteristics, known risk factors for osteoporosis and fall, and the quantitative US stiffness index were used to elaborate a predictive rule for osteoporotic fracture. Predictive values were determined by using a univariate Cox model and were adjusted with multivariate analysis. RESULTS: There were five risk factors for the incidence of osteoporotic fracture: older age (>75 years) (P < .001), low heel quantitative US stiffness index (<78%) (P < .001), history of fracture (P = .001), recent fall (P = .001), and a failed chair test (P = .029). The score points assigned to these risk factors were as follows: age, 2 (3 if age > 80 years); low quantitative US stiffness index, 5 (7.5 if stiffness index < 60%); history of fracture, 1; recent fall, 1.5; and failed chair test, 1. The cutoff value to obtain a high sensitivity (90%) was 4.5. With this cutoff, 1464 women were at lower risk (score, <4.5) and 4710 were at higher risk (score, >or=4.5) for fracture. Among the higher-risk women, 6.1% had an osteoporotic fracture, versus 1.8% of women at lower risk. Among the women who had a hip fracture, 90% were in the higher-risk group. CONCLUSION: A prediction rule obtained by using quantitative US stiffness index and four clinical risk factors helped discriminate, with high sensitivity, women at higher versus those at lower risk for osteoporotic fracture.

Measuring brain perfusion with intravoxel incoherent motion (IVIM): Initial clinical experience.

PURPOSE: To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. MATERIALS AND METHODS: We acquired high in-plane resolution (1.2 × 1.2 mm(2) ) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm(2) , in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. RESULTS: Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. CONCLUSION: Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting. J. Magn. Reson. Imaging 2014;39:624-632. © 2013 Wiley Periodicals, Inc.

Correlation between microtensile bond strength data and clinical outcome of Class V restorations.

OBJECTIVE: To determine if the results of resin-dentin microtensile bond strength (µTBS) is correlated with the outcome parameters of clinical studies on non-retentive Class V restorations. METHODS: Resin-dentin µTBS data were obtained from one test center; the in vitro tests were all performed by the same operator. The µTBS testing was performed 8h after bonding and after 6 months of storing the specimens in water. Pre-test failures (PTFs) of specimens were included in the analysis, attributing them a value of 1MPa. Prospective clinical studies on cervical restorations (Class V) with an observation period of at least 18 months were searched in the literature. The clinical outcome variables were retention loss, marginal discoloration and marginal integrity. Furthermore, an index was formulated to be better able to compare the laboratory and clinical results. Estimates of adhesive effects in a linear mixed model were used to summarize the clinical performance of each adhesive between 12 and 36 months. Spearman correlations between these clinical performances and the µTBS values were calculated subsequently. RESULTS: Thirty-six clinical studies with 15 adhesive/restorative systems for which µTBS data were also available were included in the statistical analysis. In general 3-step and 2-step etch-and-rinse systems showed higher bond strength values than the 2-step/3-step self-etching systems, which, however, produced higher values than the 1-step self-etching and the resin modified glass ionomer systems. Prolonged water storage of specimens resulted in a significant decrease of the mean bond strength values in 5 adhesive systems (Wilcoxon, p<0.05). There was a significant correlation between µTBS values both after 8h and 6 months of storage and marginal discoloration (r=0.54 and r=0.67, respectively). However, the same correlation was not found between µTBS values and the retention rate, clinical index or marginal integrity. SIGNIFICANCE: As µTBS data of adhesive systems, especially after water storage for 6 months, showed a good correlation with marginal discoloration in short-term clinical Class V restorations, longitudinal clinical trials should explore whether early marginal staining is predictive for future retention loss in non-carious cervical restorations.

Helical tomotherapy in the treatment of anal canal cancer: 3-year clinical experience

Objective: To report a single-center experience treating patients with squamous- cell carcinoma of the anal canal using helical Tomotherapy (HT) and concurrent chemotherapy (CT).Materials/Methods: From October 2007 to February 2011, 55 patients were treated with HT and concurrent CT (5-fluorouracil/capecitabin and mitomycin) for anal squamous-cell carcinoma. All patients underwent computed- tomography-based treatment planning, with pelvic and inguinal nodes receiving 36 Gy in 1.8 Gy/fraction. Following a planned 1-week break, primary tumor site and involved nodes were boosted to a total dose 59.4 Gy in 1.8 Gy/fraction. Dose-volume histograms of several organs at risk (OAR; bladder, small intestine, rectum, femoral heads, penile bulb, external genitalia) were assessed in terms of conformal avoidance. All toxicity was scored according to the CTCAE, v.3.0. HT plans and treatment were implemented using the Tomotherapy, Inc. software and hardware. For dosimetric comparisons, 3D RT and/or IMRT plans were also computed for some of the patients using the CMS planning system, for treatment with 6-18 MV photons and/or electrons with suitable energies from a Siemens Primus linear accelerator equipped with a multileaf collimator.Locoregional control and survival curves were compared with the log-rank test, and multivariate analysis by the Cox model.Results: With 360-degree-of-freedom beam projection, HT has an advantage over other RT techniques (3D or 5-field step-and-shot IMRT). There is significant improvement over 3D or 5-field IMRT plans in terms of dose conformity around the PTV, and dose gradients are steeper outside the target volume, resulting in reduced doses to OARs. Using HT, acute toxicity was acceptable, and seemed to be better than historical standards.Conclusions: Our results suggest that HT combined with concurrent CT for anal cancer is effective and tolerable. Compared to 3D RT or 5-field step-andshot IMRT, there is better conformity around the PTV, and better OAR sparing.

Wear of two denture teeth materials in vivo-2-year results.

OBJECTIVE: (1) To quantify wear of two different denture tooth materials in vivo with two study designs, (2) to relate tooth variables to vertical loss. METHODS: Two different denture tooth materials had been used (experimental material=test; DCL=control). In study 1 (split-mouth, 6 test centers) 60 subjects received complete dentures, in study 2 (two-arm, 1 test center) 29 subjects. In study 1 the mandibular dentures were supported by implants in 33% of the subjects, in study 2 only in 3% of the subjects. Impressions of the dentures were taken and poured with improved stone at baseline and after 6, 12, 18 and 24 months. Each operator evaluated the wear subjectively. Wear analysis was carried out with a laser scanning device. Maximal vertical loss of the attrition zones was calculated for each tooth cusp and tooth. A mixed linear model was used to statistically analyse the logarithmically transformed wear data. RESULTS: Due to drop-outs and unmatchable casts, only 47 subjects of study 1 and 14 of study 2 completed the 2-year recall. Overall, 75% of all teeth present could be analysed. There was no statistically difference in the overall wear between the test and control material for either study 1 or study 2. The relative increase in wear over time was similar in both study designs. However, a strong subject effect and center effect were observed. The fixed factors included in the model (time, tooth, center, etc.) accounted for 43% of the variability, whereas the random subject effect accounted for another 30% of the variability, leaving about 28% of unexplained variability. More wear was consistently recorded in the maxillary teeth compared to the mandibular teeth and in the first molar teeth compared to the premolar teeth and the second molars. Likewise, the supporting cusps showed more wear than the non-supporting cusps. The amount of wear did not depend on whether or not the lower dentures were supported by implants. The subjective wear was correct in about 67% of the cases if it is postulated that a wear difference of 100μm should be subjectively detectable. SIGNIFICANCE: The clinical wear of denture teeth is highly variable with a strong patient effect. More wear can be expected in maxillary denture teeth compared to mandibular teeth, first molars compared to premolars and supported cusps compared to non-supported cusps. Laboratory data on the wear of denture tooth materials may not be confirmed in well-structured clinical trials probably due to the large inter-individual variability.