Fracture resistance and crystal phase transformation of a one- and a two-piece zirconia implant with and without simultaneous loading and aging-An in vitro study.

OBJECTIVE: To evaluate the influence of artificial aging on the transformation propagation and fracture resistance of zirconia implants. METHODS: One-piece (with integrated implant abutment, 1P; regular diameter [4.1mm]; n = 16) and two-piece (with separate implant abutment, 2P; wide diameter [5 mm]; n = 16) zirconia implants were embedded according to ISO 14801. A two-piece titanium-zirconium implant (Ti-Zr; 4.1 mm diameter) served as a control (n = 16). One subgroup (n = 8) of each system was simultaneously dynamically loaded (107 cycles; 98N) and hydrothermally aged (85°C, 58 days), while the other subgroup (n = 8) remained untreated. Finally, specimens were statically loaded to fracture. Potential crystal phase transformation was examined at cross sections using scanning electron microscopy (SEM). A multivariate linear regression model was applied for statistical analyses. RESULTS: The fracture resistance of 1P (1,117 [SD = 38] N; loaded/aged: 1,009 [60] N), 2P (850 [36] N; loaded/aged: 799 [84] N), and Ti-Zr implants (1,338 [205] N; loaded/aged: 1,319 [247] N) was not affected significantly by loading/aging (p = .171). However, when comparing the systems, they revealed significant differences independent of loading/aging (p ≤ .001). Regarding the crystal structure, a transformation zone was observed in SEM images of 1P only after aging, while 2P showed a transformation zone even before aging. After hydrothermal treatment, an increase of this monoclinic layer was observed in both systems. CONCLUSIONS: The Ti-Zr control implant showed higher fracture resistance compared to both zirconia implants. Loading/aging had no significant impact on the fracture resistance of both zirconia implants. The wide-body 2P zirconia implant was weaker than the regular body 1P implant.

In vitro evaluation of the cariogenic potential of rebaudioside A compared to sucrose and xylitol.

OBJECTIVES: The aim of the present study was to evaluate the growth and acid synthesis of cariogenic pathogens in vitro when rebaudioside A was the sole source of carbon, compared to sucrose, xylitol, and a commercial sweetener containing rebaudioside A. MATERIALS AND METHODS: First, sucrose or sugar substitutes were added to human saliva and the pH was measured over 10 h. Subsequently, the growth and acid synthesis efficiency of Streptococcus mutans, Streptococcus sobrinus, Streptococcus oralis, Lactobacillus rhamnosus, Lactobacillus paracasei, and Candida albicans were investigated: after adding them to minimal culture media containing only one of the carbon sources, the optical density and pH were determined over 10 h. RESULTS: A significant pH drop only occurred in the sucrose group of human saliva whereas no differences were found between the sugar substitute groups. The individual strains of caries pathogens showed significantly lower growth rates and less acid synthesis in the sugar replacement groups, in comparison to sucrose. However, these groups also showed bacterial growth and a decline in pH. CONCLUSION: Xylitol appeared to be superior to rebaudioside A regarding the inhibition of mutans streptococci. The results for the remaining microorganisms indicate that rebaudioside A causes a similar or lower acid synthesis than xylitol. As saliva contains buffer systems, the metabolism of rebaudioside A did not seem to shift the equilibrium to demineralization. CLINICAL RELEVANCE: Rebaudioside A may not be suitable as a targeted Streptococcus mutans treatment, but it could contribute to a reduction of caries risk as a replacement for sucrose.

A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis.

BACKGROUND: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. OBJECTIVES: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. METHODS: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. RESULTS: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. CONCLUSIONS: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID.

The case-crossover design via penalized regression.

BACKGROUND: The case-crossover design is an attractive alternative to the classical case-control design which can be used to study the onset of acute events if the risk factors of interest vary in time. By comparing exposures within cases at different time periods, the case-crossover design does not rely on control subjects which can be difficult to acquire. However, using the standard method of maximum likelihood, resulting risk estimates can be heavily biased when the prevalence to risk factors is very low (or very high). METHODS: To overcome the problem of low risk factor prevalences, penalized conditional logistic regression via the lasso (least absolute shrinkage and selection operator) has been proposed in the literature as well as related methods such as the Firth correction. We apply and compare several penalized regression approaches in the context of a case-crossover analysis of the European Study of Severe Cutaneous Adverse Reactions (EuroSCAR; 1997-2001). RESULTS: Out of 30 drugs, standard methods only correctly classified 17 drugs (including some highly implausible risk estimates), while penalized methods correctly classified 22 drugs. CONCLUSION: Penalized methods generally yield better risk classifications and much more plausible risk estimates for the EuroSCAR study than standard methods. As these novel techniques can be easily implemented using available R packages, we encourage routine use of penalized conditional logistic regression for case-crossover data.

Assessment of the "case-chaos" design as an adjunct to the case-control design.

In 2012, a novel case series method dubbed the "case-chaos" design was proposed as an alternative to case-control studies, whereby controls are artificially created by permutating the exposure information of the cases. Our aim in the current work was to further evaluate the case-chaos method. Using a theoretical example of 2 risk factors, we demonstrated that the case-chaos design yields risk estimations for which the odds ratios obtained for every risk factor are in the same ascending order as the risk factors' exposure prevalences in the case group. Applying the method to data from the European Study of Severe Cutaneous Adverse Reactions (EuroSCAR; 1997-2001), we were not able to obtain sensible results but instead produced results as predicted by our theoretical assessment. We therefore claim that the method is equivalent to declaring risk solely on the basis of prevalences obtained in cases. While the proposers of the case-chaos method view it as a useful adjunct, we show that it cannot produce sensible estimates.

Estimating incidence and attributable length of stay of healthcare-associated infections-Modeling the Swiss point-prevalence survey.

OBJECTIVES: In 2017, a point-prevalence survey was conducted with 12,931 patients in 96 hospitals across Switzerland as part of the national strategy to prevent healthcare-associated infections (HAIs). We present novel statistical methods to assess incidence proportions of HAI and attributable length-of-stay (LOS) in point-prevalence surveys. METHODS: Follow-up data were collected for a subsample of patients and were used to impute follow-up data for all remaining patients. We used weights to correct length bias in logistic regression and multistate analyses. Methods were also tested in simulation studies. RESULTS: The estimated incidence proportion of HAIs during hospital stay and not present at admission was 2.3% (95% confidence intervals [CI], 2.1-2.6), the most common type being lower respiratory tract infections (0.8%; 95% CI, 0.6-1.0). Incidence proportion was highest in patients with a rapidly fatal McCabe score (7.8%; 95% CI, 5.7-10.4). The attributable LOS for all HAI was 6.4 days (95% CI, 5.6-7.3) and highest for surgical site infections (7.1 days, 95% CI, 5.2-9.0). It was longest in the age group of 18-44 years (9.0 days; 95% CI, 5.4-12.6). Risk-factor analysis revealed that McCabe score had no effect on the discharge hazard after infection (hazard ratio [HR], 1.21; 95% CI, 0.89-1.63). Instead, it only influenced the infection hazard (HR, 1.84; 95% CI, 1.39-2.43) and the discharge hazard prior to infection (HR, 0.73; 95% CI, 0.66-0.82). CONCLUSIONS: In point-prevalence surveys with limited follow-up data, imputation and weighting can be used to estimate incidence proportions and attributable LOS that would otherwise require complete follow-up data.

Non-Precious Metal Alloy Double Crown-Retained Removable Partial Dentures: A Cross-Sectional In Vivo Investigation.

(1) Background: An alternative material to precious metal alloys are non-precious metal alloys. The material properties of these are different and, therefore, their clinical, biological and mechanical behaviors may also differ. Hence, the purpose of this in vivo investigation was to analyze the clinical and patient-reported outcomes of patients restored with non-precious metal alloy double crown-retained removable partial dentures (NP-D-RPDs). (2) Methods: Partially edentulous patients were restored with non-precious metal alloy partially veneered NP-D-RPDs. Survival rates, success rates, failures and patient-reported outcomes were investigated and statistically evaluated. (3) Results: A total of 61 patients (65.6 ± 10.8 years) were included and clinically and radiographically examined. The mean follow-up time was 25.2 ± 16.5 months. In total, 82 NP-D-RPDs and 268 abutment teeth were examined. The overall survival rate of the NP-D-RPDs was 100% after a mean follow-up time of 2.1 years. The overall success rate was 68.3%. The overall satisfaction with the NP-D-RPDs was 94.3%. (4) Conclusions: Non-precious metal alloy partially veneered NP-D-RPDs seem to be an efficient alternative to precious metal alloy RPDs with excellent patient-reported outcomes.

Inverse Probability Weighting Enhances Absolute Risk Estimation in Three Common Study Designs of Nosocomial Infections.

Purpose: When studying nosocomial infections, resource-efficient sampling designs such as nested case-control, case-cohort, and point prevalence studies are preferred. However, standard analyses of these study designs can introduce selection bias, especially when interested in absolute rates and risks. Moreover, nosocomial infection studies are often subject to competing risks. We aim to demonstrate in this tutorial how to address these challenges for all three study designs using simple weighting techniques. Patients and Methods: We discuss the study designs and explain how inverse probability weights (IPW) are applied to obtain unbiased hazard ratios (HR), odds ratios and cumulative incidences. We illustrate these methods in a multi-state framework using a dataset from a nosocomial infections study (n = 2286) in Moscow, Russia. Results: Including IPW in the analysis corrects the unweighted naïve analyses and enables the estimation of absolute risks. Resulting estimates are close to the full cohort estimates using substantially smaller numbers of patients. Conclusion: IPW is a powerful tool to account for the unequal selection of controls in case-cohort, nested case-control and point prevalence studies. Findings can be generalized to the full population and absolute risks can be estimated. When applied to a multi-state model, competing risks are also taken into account.

Prognostic impact of invasive exercise haemodynamics in patients with severe mitral regurgitation.

OBJECTIVES: Abnormal invasive exercise haemodynamics in asymptomatic patients with severe mitral regurgitation were associated with higher regurgitation burden. We analysed the association between parameters of invasive exercise testing with mortality and valve surgery compared to guideline defined non-invasive criteria. METHODS: This single centre, retrospective cohort study assesses the association of invasive exercise haemodynamics and mortality with and without surgery in patients with severe mitral regurgitation and normal ejection fraction (≥55%) as primary outcome. The secondary outcome was the need for mitral valve surgery in 113 asymptomatic patients primarily managed conservatively. RESULTS: We identified 314 patients [age 59 years (standard deviation 13), 27% female] with available exercise haemodynamics with a median follow-up of 8.2 (interquartile range 5.2-11.2) years. Five-year survival rate was 93.0%. Pulmonary capillary wedge pressure at maximum exercise >30 mmHg was the only parameter independently associated with mortality after adjustment for age and guideline criteria [hazard ratio (HR) 2.7 (1.3-5.6), P = 0.007]. In the 113 patients primarily managed conservatively, maximum pulmonary capillary wedge pressure was independently associated with mitral valve surgery during follow-up in multivariable analysis (HR 2.10 (1.32-3.34), P = 0.002; after adjustment for workload and weight: HR 1.31 (1.14-1.52), P < 0.001], whereas systolic pulmonary artery pressure and current guideline criteria were not. Adding maximum pulmonary capillary wedge pressure >25 mmHg improved the predictive power of current guideline criteria for surgery (area under the curve 0.61-0.68, P = 0.02). CONCLUSIONS: Invasive exercise haemodynamics predict mortality and improve prognostic information about surgery during follow-up derived from current guideline criteria in asymptomatic patients with severe mitral regurgitation.

Mechanical Stability of Screw-Retained Monolithic and Bi-layer Posterior Hybrid Abutment Crowns after Thermomechanical Loading: An In Vitro Study.

To evaluate the failure-load and survival-rate of screw-retained monolithic and bi-layered crowns bonded to titanium-bases before and after mouth-motion fatigue, 72 titanium-implants (SICvantage-max, SIC-invent-AG) were restored with three groups (n = 24) of screw-retained CAD/CAM implant-supported-single-crowns (ISSC) bonded to titanium-bases: porcelain-fused-to-metal (PFM-control), porcelain-fused-to-zirconia (PFZ-test) and monolithic LDS (LDS-test). Half of the specimens (n = 12/group) were subjected to fatigue in a chewing-simulator (1.2 million cycles, 198 N, 1.67 Hz, thermocycling 5-55 °C). All samples were exposed to single-load-to-failure without (PFM0, PFZ0, LDS0) or with fatigue (PFM1, PFZ1, LDS1). Comparisons were statistically analyzed with t-tests and regression-models and corrected for multiple-testing using the Student-Neuman-Keuls method. All PFM and LDS crowns survived fatigue exposure, whereas 16.7% of PFZ showed chipping failures. The mean failure-loads (±SD) were: PFM0: 2633 ± 389 N, PFM1: 2349 ± 578 N, PFZ0: 2152 ± 572 N, PFZ1: 1686 ± 691 N, LDS0: 2981 ± 798 N, LDS1: 2722 ± 497 N. Fatigue did not influence load to failure of any group. PFZ ISSC showed significantly lower failure-loads than monolithic-LDS regardless of artificial aging (p < 0.05). PFM ISSC showed significantly higher failure loads after fatigue than PFZ (p = 0.032). All ISSC failed in a range above physiological chewing forces. Premature chipping fractures might occur in PFZ ISSC. Monolithic-LDS ISSC showed high reliability as an all-ceramic material for screw-retained posterior hybrid-abutment-crowns.

Penalized logistic regression with low prevalence exposures beyond high dimensional settings.

Estimating and selecting risk factors with extremely low prevalences of exposure for a binary outcome is a challenge because classical standard techniques, markedly logistic regression, often fail to provide meaningful results in such settings. While penalized regression methods are widely used in high-dimensional settings, we were able to show their usefulness in low-dimensional settings as well. Specifically, we demonstrate that Firth correction, ridge, the lasso and boosting all improve the estimation for low-prevalence risk factors. While the methods themselves are well-established, comparison studies are needed to assess their potential benefits in this context. This is done here using the dataset of a large unmatched case-control study from France (2005-2008) about the relationship between prescription medicines and road traffic accidents and an accompanying simulation study. Results show that the estimation of risk factors with prevalences below 0.1% can be drastically improved by using Firth correction and boosting in particular, especially for ultra-low prevalences. When a moderate number of low prevalence exposures is available, we recommend the use of penalized techniques.

Osseointegration of zirconia dental implants in animal investigations: A systematic review and meta-analysis.

OBJECTIVE: To determine the osseointegration rate of zirconium dioxide (ZrO2) dental implants in preclinical investigations. DATA: Data on the osseointegration rate was extracted considering the bone to implant contact (BIC), removal torque analysis (RTQ) and push-in tests. Meta analyses were conducted using multilevel multivariable mixed-effects linear regression models. The Sidák method was used in case of multiple testing. SOURCES: An electronic screening of the literature (MEDLINE/Pubmed, Cochrane Library and Embase) and a supplementary manual search were performed. Animal investigations with a minimum sample size of 3 units evaluating implants made of zirconia (ZrO2) or its composites (ZrO2>50vol.%) were included. STUDY SELECTION: The search provided 4577 articles, and finally 54 investigations were included and analyzed. Fifty-two studies included implants made from zirconia, 4 zirconia composite implants and 37 titanium implants. In total, 3435 implants were installed in 954 animals. CONCLUSIONS: No significant influence of the evaluated bulk materials on the outcomes of interest could be detected. When comparing different animal models, significant differences for the evaluated variables could be found. These results might be of interest for the design of further animal investigations.

Stability and aging resistance of a zirconia oral implant using a carbon fiber-reinforced screw for implant-abutment connection.

OBJECTIVE: To investigate the long-term stability of a metal-free zirconia two-piece implant assembled with a carbon fiber-reinforced (CRF) screw by means of transformation propagation, potential changes in surface roughness, the gap size of the implant-abutment connection, and fracture load values. METHODS: In a combined procedure, two-piece implants made from alumina-toughened zirconia were dynamically loaded (107 cycles) and hydrothermally aged (85°, 60days). Implants made from titanium (Ti) and a titanium-zirconium (TiZr) alloy with a titanium abutment screw served as control. Transformation propagation (ATZ) and gap size of the IAC were monitored at cross-sections by scanning electron microscopy (SEM). Furthermore, changes in surface roughness of ATZ implants were measured. Finally, implants were statically loaded to fracture. Linear regression models and pairwise comparisons were used for statistical analyses. RESULTS: Independent of the implant bulk material, dynamic loading/hydrothermal aging did not decrease fracture resistance (p=0.704). All test and control implants fractured at mean loads >1100N. Gap size of the IAC remained stable (<5µm) or decreased. None of the CFR screws fractured during static or dynamic loading. Monoclinic layer thickness of ATZ implants increased by 2-3µm at surfaces exposed to water, including internal surfaces of the IAC. No changes in surface roughness were observed. SIGNIFICANCE: Combined hydrothermal aging and dynamic loading did not affect the above-mentioned parameters of the evaluated two-piece ATZ implant. Mean fracture loads >1100N suggest a reliable clinical application.

European Cross-Sectional Survey of Current Care Practices for Duchenne Muscular Dystrophy Reveals Regional and Age-Dependent Differences.

BACKGROUND: Publication of comprehensive clinical care guidelines for Duchenne muscular dystrophy (DMD) in 2010 was a milestone for DMD patient management. Our CARE-NMD survey investigates the neuromuscular, medical, and psychosocial care of DMD patients in Europe, and compares it to the guidelines. METHODS: A cross-sectional survey of 1677 patients contacted via the TREAT-NMD patient registries was conducted using self-report questionnaires in seven European countries. RESULTS: Survey respondents were 861 children and 201 adults. Data describe a European DMD population with mean age of 13.0 years (range 0.8-46.2) of whom 53% had lost ambulation (at 10.3 years of age, median). Corticosteroid medication raised the median age for ambulatory loss from 10.1 years in patients never medicated to 11.4 years in patients who received steroids (p < 0.0001). The majority of patients reported receiving care in line with guidelines, although we identified significant differences between countries and important shortcomings in prevention and treatment. Summarised, 35% of patients aged≥ nine years received no corticosteroid medication, 24% of all patients received no regular physiotherapy, echocardiograms were not performed regularly in 22% of patients, pulmonary function was not regularly assessed in 71% of non-ambulatory patients. Patients with regular follow-up by neuromuscular specialists were more likely to receive care according to guidelines, were better satisfied, and experienced shorter unplanned hospitalization periods.