Relevance of in vitro tests of adhesive and composite dental materials, a review in 3 parts. Part 1: Approval requirements and standardized testing of composite materials according to ISO specifications

The first part of this three-part review on the relevance of laboratory testing of composites and adhesives deals with approval requirements for composite materials. We compare the in vivo and in vitro literature data and discuss the relevance of in vitro analyses. The standardized ISO protocols are presented, with a focus on the evaluation of physical parameters. These tests all have a standardized protocol that describes the entire test set-up. The tests analyse flexural strength, depth of cure, susceptibility to ambient light, color stability, water sorption and solubility, and radiopacity. Some tests have a clinical correlation. A high flexural strength, for instance, decreases the risk of fractures of the marginal ridge in posterior restorations and incisal edge build-ups of restored anterior teeth. Other tests do not have a clinical correlation or the threshold values are too low, which results in an approval of materials that show inferior clinical properties (e.g., radiopacity). It is advantageous to know the test set-ups and the ideal threshold values to correctly interpret the material data. Overall, however, laboratory assessment alone cannot ensure the clinical success of a product.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

Clinical research projects at a German medical faculty: follow-up from ethical approval to publication and citation by others

BACKGROUND: Only data of published study results are available to the scientific community for further use such as informing future research and synthesis of available evidence. If study results are reported selectively, reporting bias and distortion of summarised estimates of effect or harm of treatments can occur. The publication and citation of results of clinical research conducted in Germany was studied. METHODS: The protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) in 2000 were analysed. Published full articles in several databases were searched and investigators contacted. Data on study and publication characteristics were extracted from protocols and corresponding publications. RESULTS: 299 study protocols were included. The most frequent study design was randomised controlled trial (141; 47%), followed by uncontrolled studies (61; 20%), laboratory studies (30; 10%) and non-randomised studies (29; 10%). 182 (61%) were multicentre studies including 97 (53%) international collaborations. 152 of 299 (51%) had commercial (co-)funding and 46 (15%) non-commercial funding. 109 of the 225 completed protocols corresponded to at least one full publication (total 210 articles); the publication rate was 48%. 168 of 210 identified publications (80%) were cited in articles indexed in the ISI Web of Science. The median was 11 citations per publication (range 0-1151). CONCLUSIONS: Results of German clinical research projects conducted are largely underreported. Barriers to successful publication need to be identified and appropriate measures taken. Close monitoring of projects until publication and adequate support provided to investigators may help remedy the prevailing underreporting of research.

Strategies to increase the use and approval of gender-fair language

When masculine forms are used to refer to men and women, this causes male-biased cognitive representations and behavioral consequences, as numerous studies have shown. This effect can be avoided or reduced with the help of gender-fair language. In this talk, we will present different approaches that aim at influencing people’s use of and attitudes towards gender-fair language. Firstly, we tested the influence of gender-fair input on people’s own use of gender-fair language. Based on Irmen and Linner’s (2005) adaptation of the scenario mapping and focus approach (Sanford & Garrod, 1998), we found that after reading a text with gender-fair forms women produced more gender-fair forms than women who read gender-neutral texts or texts containing masculine generics. Men were not affected. Secondly, we examined reactions to arguments which followed the Elaboration Likelihood Model (Petty &Cacioppo, 1986). We assumed that strong pros and cons would be more effective than weak arguments or control statements. The results indicated that strong pros could convince some, but not all participants, suggesting a complex interplay of diverse factors in reaction to attempts at persuasion. The influence of people’s initial characteristics will be discussed. Currently, we are investigating how self-generated refutations, in addition to arguments, may influence initial attitudes. Based on the resistance appraisal hypothesis (Tormala, 2008), we assume that individuals are encouraged in their initial attitude if they manage to refute strong counter-arguments. The results of our studies will be discussed regarding their practical implications.

Quantitative T2 mapping of knee cartilage: differentiation of healthy control cartilage and cartilage repair tissue in the knee with unloading - initial results

Purpose: To prospectively determine on T2 cartilage maps the effect of unloading during a clinical magnetic resonance (MR) examination in the postoperative follow-up of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint. Materials and Methods: Ethical approval for this study was provided by the local ethics commission, and written informed consent was obtained. Thirty patients (mean age, 35.4 years +/- 10.5) with a mean postoperative follow-up period of 29.1 months +/- 24.4 were enrolled. A multiecho spin-echo T2-weighted sequence was performed at the beginning (early unloading) and end (late unloading) of the MR examination, with an interval of 45 minutes. Mean and zonal region of interest T2 measurements were obtained in control cartilage and cartilage repair tissue. Statistical analysis of variance was performed. Results: The change in T2 values of control cartilage (early unloading, 50.2 msec +/- 8.4; late unloading, 51.3 msec +/- 8.5) was less pronounced than the change in T2 values of cartilage repair tissue (early unloading, 51.8 msec +/- 11.7; late unloading, 56.1 msec +/- 14.4) (P = .024). The difference between control cartilage and cartilage repair tissue was not significant for early unloading (P = .314) but was significant for late unloading (P = .036). Zonal T2 measurements revealed a higher dependency on unloading for the superficial cartilage layer. Conclusion: Our results suggest that T2 relaxation can be used to assess early and late unloading values of articular cartilage in a clinical setting and that the time point of the quantitative T2 measurement affects the differentiation between native and abnormal articular cartilage. (c) RSNA, 2010.

Deposition, imaging, and clearance: what remains to be done?

Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.

Relevance of In-vitro Tests of Adhesive and Composite Dental Materials. A Review in 3 Parts. Part 2: Non-standardized tests of composite materials

Summary The first part of this review examined ISO approval requirements and in vitro testing. In the second part, non-standardized test methods for composite materials are presented and discussed. Physical tests are primarily described. Analyses of surface gloss and alterations, as well as aging simulations of dental materials are presented. Again, the importance of laboratory tests in determining clinical outcomes is evaluated. Differences in the measurement protocols of the various testing institutes and how these differences can in?uence the results are also discussed. Because there is no standardization of test protocols, the values determined by different institutes cannot be directly compared. However, the ranking of the tested materials should be the same if a valid protocol is applied by different institutes. The modulus of elasticity, the expansion after water sorption, and the polishability of the material are all clinically relevant, whereas factors measured by other test protocols may have no clinical correlation. The handling properties of the materials are highly dependent on operators' preferences. Therefore, no standard values can be given.

The in vitro effects of dexamethasone, insulin and triiodothyronine on degenerative human intervertebral disc cells under normoxic and hypoxic conditions

Degeneration of intervertebral discs (IVD) is one of the main causes of back pain and tissue engineering has been proposed as a treatment. Tissue engineering requires the use of highly expensive growth factors, which might, in addition, lack regulatory approval for human use. In an effort to find readily available differentiation factors, we tested three molecules – dexamethasone, triiodothyronine (T3) and insulin – on human IVD cells isolated after surgery, expanded in vitro and transferred into alginate beads. Triplicates containing 40 ng/ml dexamethasone, 10 nM T3 and 10 µg/ml insulin, together with a positive control (10 ng/mL transforming growth factor (TGF)-beta 1), were sampled weekly over six weeks and compared to a negative control. Furthermore, we compared the results to cultures with optimized chondrogenic media and under hypoxic condition (2% O2). Glycosaminoglycan (GAG) determination by Alcian Blue assay and histological staining showed dexamethasone to be more effective than T3 and insulin, but less than TGF-beta1. DNA quantification showed that only dexamethasone stimulated cell proliferation. qPCR demonstrated that TGF-beta1 and the optimized chondrogenic groups increased the expression of collagen type II, while aggrecan was stimulated in cultures containing dexamethasone. Hypoxia increased GAG accumulation, collagen type II and aggrecan expression, but had no effect on or even lowered cell number. In conclusion, dexamethasone is a valuable and cost-effective molecule for chondrogenic and viability induction of IVD cells under normoxic and hypoxic conditions, while insulin and T3 did not show significant differences.

"Drug mules" as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

PURPOSE: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox(®)) in the detection of internal cocaine containers. METHODS: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16-45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT=35, nDR=70, nLSDR=30. An overall calculation of all "drug mules" and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. RESULTS: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. CONCLUSIONS: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

[Mechanical Thrombectomy for Acute Ischemic Stroke.]

The therapy of acute ischemic stroke aims at fast recanalization of the occluded brain vessel. In contrast to intravenous thrombolysis (IVT), endovascular approaches yield higher recanalization rates especially in large vessel occlusions. Mechanical thrombectomy with the Merci Retriever received FDA approval in 2004 as an adjunct to IVT or in the case of failed recanalization after IVT. The time window for treatment is 8 h from stroke onset. However, the recanalization rate was 55 %, still leaving space for further improvement. In addition to the Merci Retriever, the Penumbra System received FDA approval in 2008. The newest endovascular approach comprising retrievable intracranial stents results in an increased recanalization rate exceeding 90 % and has markedly reduced the time to recanalization. On the other hand, the complication rate has not increased yet. These promising results suggest a combined therapy for acute ischemic stroke. In a first step IVT can be started independently of the size of the treating hospital and in a next step the patient is transferred to a neuroradiological center. If vessel occlusion persists, additional endovascular recanalization is performed (bridging concept). Patients who don't qualify for IVT are candidates for mechanical thrombectomy up to 8 h after stroke onset.

Recent developments for surgical aortic valve replacement: the concept of sutureless valve technology

Aortic stenosis has become the most frequent type of valvular heart disease in Europe and North America and presents in the large majority of patients as calcified aortic stenosis in adults of advanced age. Surgical aortic valve replacement has been recognized to be the definitive therapy which improves considerably survival for severe aortic stenosis since more than 40 years. In the most recent period, operative mortality of isolated aortic valve replacement for aortic stenosis varies between 1–3% in low-risk patients younger than 70 years and between 4 and 8% in selected older adults. Long-term survival following aortic valve replacement is close to that observed in a control population of similar age. Numerous observational studies have consistently demonstrated that corrective surgery in symptomatic patients is invariably followed by a subjective improvement in quality of life and a substantial increase in survival rates. More recently, transcatheter aortic valve implantation (TAVI) has been demonstrated to be feasible in patients with high surgical risk using either a retrograde transfemoral or transsubclavian approach or an antegrade, transapical access. Reported 30-day mortality ranges between 5 and 15%) and is acceptable when compared to the risk predicted by the logistic EuroSCORE (varying between 20 and 35%) and the STS Score, although the EuroScore has been shown to markedly overestimate the effective operative risk. One major concern remains the high rate of paravalvular regurgitation which is observed in up to 85% of the patients and which requires further follow-up and critical evaluation. In addition, long-term durability of these valves with a focus on the effects of crimping remains to be addressed, although 3-5 year results are promising. Sutureless biological valves were designed to simplify and significantly accelerate the surgical replacement of a diseased valve and allow complete excision of the calcified native valve. Until now, there are 3 different sutureless prostheses that have been approved. The 3f Enable valve from ATS-Medtronic received CE market approval in 2010, the Perceval S from Sorin during Q1 of 2011 and the intuity sutureless prosthesis from Edwards in 2012. All these devices aim to facilitate valve surgery and therefore have the potential to decrease the invasivness and to shorten the conventional procedure without compromise in term of excision of the diseased valve. This review summarizes the history and the current knowledge of sutureless valve technology.

[Adapted and Standardised Patient Management in the Treatment of Neovascular AMD in the Outpatient Setting of a University Eye Hospital.]

Visual results in treating neovascular age-related macular degeneration (AMD) using intravitreal injected anti-VEGF (IVT) clearly depend on injection frequency. Regarding to the European approval Ranibizumab has to be used only in cases of recurrent visual loss after the loading phase. In contrast monthly treatment--as also provided in the ANCHOR and MARINA studies--is generally allowed in Switzerland. However, it is commonly tried to reduce the injection frequency because of the particular cost situation in all health systems and of cause also due to the necessary strict monitoring and reinjection regimes, which raise management problems with increasing patient numbers. In this article the special treatment regimes of our University Eye Hospital is presented, in which a reduced injection frequency basically leads to the same increased and stable visual results as in ANCHOR and MARINA; however, needing significantly more injections as generally provided in other countries of Europe. The main focus for achieving this in a large number of patients is placed on re-structuring our outpatient flow for IVT patients with particular emphasis on patient separation and standardisation of treatment steps leading to significantly reduced time consumption per patient. Measurements of timing and patient satisfaction before and after restructuring underline its importance in order to be able to treat more patients at a high quality even in the future. The exceptional importance of spectral domain OCT measurements as the most important criterium for indicating re-treatment is illustrated.

Hereditary angioedema (HAE) in children and adolescents--a consensus on therapeutic strategies

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.