Time-to-event estimands and loss to follow-up in oncology in light of the estimands guidance.

Time-to-event estimands are central to many oncology clinical trials. The estimands framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest and requires predefining the handling of intercurrent events (ICEs) that occur after treatment initiation and "affect either the interpretation or the existence of the measurements associated with the clinical question of interest." We discuss a practical problem in clinical trial design and execution, that is, in some clinical contexts it is not feasible to systematically follow patients to an event of interest. Loss to follow-up in the presence of intercurrent events can affect the meaning and interpretation of the study results. We provide recommendations for trial design, stressing the need for close alignment of the clinical question of interest and study design, impact on data collection, and other practical implications. When patients cannot be systematically followed, compromise may be necessary to select the best available estimand that can be feasibly estimated under the circumstances. We discuss the use of sensitivity and supplementary analyses to examine assumptions of interest.

Management of oxidative stress for cell therapy through combinational approaches of stem cells, antioxidants, and photobiomodulation.

Over the recent decades, stem cell-based therapies have been considered as a beneficial approach for the treatment of various diseases. In these types of therapies, the stem cells and their products are used as treating agents. Despite the helpful efficacy of stem cell-based therapies, there may be challenges. Oxidative stress (OS) is one of these challenges that can affect the therapeutic properties of stem cells. Therefore, it seems that employing strategies for the reduction of OS in combination with stem cell therapy can lead to better results of these therapies. Based on the available evidence, antioxidant therapy and photobiomodulation (PBM) are strategies that can regulate the OS in the cells. Antioxidant therapy is a method in which various antioxidants are used in the therapeutic processes. PBM is also the clinical application of light that gained importance in medicine. Antioxidants and PBM can regulate OS by the effect on mitochondria as an important source of OS in the cells. Considering the importance of OS in pathologic pathways and its effect on the treatment outcomes of stem cells, in the present review first the stem cell therapy and effects of OS on this type of therapy are summarized. Then, antioxidant therapy and PBM as approaches for reducing OS with a focus on mitochondrial function are discussed. Also, a novel combination treatment with the hope of achieving better and more stable outcomes in the treatment process of diseases is proposed.

Duration of and time to response in oncology clinical trials from the perspective of the estimand framework.

Duration of response (DOR) and time to response (TTR) are typically evaluated as secondary endpoints in early-stage clinical studies in oncology when efficacy is assessed by the best overall response and presented as the overall response rate. Despite common use of DOR and TTR in particular in single-arm studies, the definition of these endpoints and the questions they are intended to answer remain unclear. Motivated by the estimand framework, we present relevant scientific questions of interest for DOR and TTR and propose corresponding estimand definitions. We elaborate on how to deal with relevant intercurrent events which should follow the same considerations as implemented for the primary response estimand. A case study in mantle cell lymphoma illustrates the implementation of relevant estimands of DOR and TTR. We close the paper with practical recommendations to implement DOR and TTR in clinical study protocols.

Group 4 ITI Consensus Report: Patient benefits following implant treatment in partially and fully edentulous patients.

OBJECTIVES: The aim of Working Group 4 was to address patient benefits associated with implant dentistry. Focused questions on (a) dental patient-reported outcomes (dPROs), (b) improvement in orofacial function, and (c) preservation of orofacial tissues in partially and fully edentulous patients following provision of implant-retained/supported dental prostheses were addressed. MATERIALS AND METHODS: Three systematic reviews formed the basis for discussion. Participants developed statements and recommendations determined by group consensus based on the findings of the systematic reviews. These were then presented and accepted following further discussion and modifications as required by the plenary of the 7th ITI Consensus Conference, taking place in 2023 in Lisbon, Portugal. RESULTS: Edentulous patients wearing complete dentures (CD) experience substantial improvements in overall dPROs and orofacial function following treatment with either complete implant-supported fixed dental prostheses (CIFDP) or implant overdentures (IODs). With respect to dPROs, mandibular IODs retained by two implants are superior to IODs retained by one implant. However, increasing the number of implants beyond two, does not further improve dPROs. In fully edentulous patients, rehabilitation with CIFDP or IOD is recommended to benefit the preservation of alveolar bone and masseter muscle thickness. CONCLUSIONS: Completely edentulous patients benefit substantially when at least the mandible is restored using an CIFDP or an IOD compared to CD. In fully edentulous patients, implant prostheses are the best option for tooth replacement. The availability of this treatment modality should be actively promoted in all edentulous communities, including those with limited access and means.

Effect of dental implant therapy on the preservation of orofacial tissues: A systematic review and meta-analysis.

OBJECTIVE: Fundamentally, this review addresses the following question: In partially or fully edentulous patients, do implant-supported dental prostheses preserve orofacial tissues when compared to conventional prostheses or no therapy? MATERIALS AND METHODS: This study was conducted according to the 2020 PRISMA guidelines for systematic reviews. Electronic searches were conducted at PubMed and Embase databases followed by manual search. Clinical studies comparing the effect of implant-supported prostheses with conventional rehabilitation or no treatment on alveolar bone resorption, remaining teeth, and jaw muscle thickness were considered for inclusion. A qualitative synthesis was conducted with all included studies, and data from selected studies were pooled quantitatively to perform a meta-analysis. RESULTS: A total of 14 studies were selected for analysis. Six studies reported on the effect of implant therapy on alveolar bone resorption (n = 453), six on the remaining teeth (n = 1014), while four studies evaluated masseter muscle thickness (n = 158). The results of the meta-analyses assessing alveolar bone resorption in the posterior mandible and in the anterior area of the maxilla, both fixed and random effects models, yielded no benefit of rehabilitation with implant-supported prostheses when compared to conventional prostheses. For masseter bone thickness, however, a significant benefit for implant-supported prosthesis was observed. CONCLUSIONS: This systematic review and meta-analysis were unable to unequivocally answer the focus question. There are some indicators of the benefit of implant-supported prostheses over conventional prostheses or no therapy in preserving orofacial tissues, particularly for masseter muscle thickness. However, the evidence is still insufficient to confirm such perception.

Breeding from 1891 to 2010 did not increase the content of amylase/trypsin-inhibitors in wheat (Triticum aestivum).

The prevalence of hypersensitivities towards wheat has increased in the last decades. Apart from celiac disease these include allergic and other inflammatory reactions summarized under the term non-celiac wheat sensitivity. One suspected trigger is the family of amylase/trypsin-inhibitors (ATIs), non-gluten proteins that are prominent wheat allergens and that activate the toll-like receptor 4 on intestinal immune cells to promote intestinal and extra-intestinal inflammation. We therefore quantified 13 ATIs in 60 German hexaploid winter wheat cultivars originating from 1891 to 2010 and harvested in three years by targeted liquid chromatography-tandem mass spectrometry combined with stable isotope dilution assay using specific marker peptides as internal standards. The total ATI content and that of the two major ATIs 0.19 and CM3 did not change from old cultivars (first registered from 1891 to 1950) to modern cultivars (1951-2010). There were also no significant changes in ATI distribution.

Quantification of follow-up time in oncology clinical trials with a time-to-event endpoint: Asking the right questions.

For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some quantification of the amount of follow-up. Typically, a median of some loosely defined quantity is reported. However, whatever median is reported, is typically not answering the question(s) trialists actually have in terms of follow-up quantification. In this paper, inspired by the estimand framework, we formulate a comprehensive list of relevant scientific questions that trialists have when reporting time-to-event data. We illustrate how these questions should be answered, and that reference to an unclearly defined follow-up quantity is not needed at all. In drug development, key decisions are made based on randomized controlled trials, and we therefore also discuss relevant scientific questions not only when looking at a time-to-event endpoint in one group, but also for comparisons. We find that different thinking about some of the relevant scientific questions around follow-up is required depending on whether a proportional hazards assumption can be made or other patterns of survival functions are anticipated, for example, delayed separation, crossing survival functions, or the potential for cure. We conclude the paper with practical recommendations.

The 'Myth of Zero-COVID' Nation: A Digital Ethnography of Expats' Survival Amid Shanghai Lockdown during the Omicron Variant Outbreak.

This study presents a digital ethnography of expats' survival amid the Shanghai lockdown during the Omicron variant outbreak. This study drew insights from studies on resilience and secondary coping within the context of global migration to comprehend the diverse emotional challenges faced by expats in a series of lockdowns and persistent nucleic acid amplification tests. Thus, this study asks what the major emotional challenges expats faced and what sources of social support they could draw from citizens in their host country during the Shanghai lockdown. Accordingly, this study collected WeChat group conversations to draw empirical findings, promoted scholarly conversations about fundamental survival necessity, and traced the process for establishing intercultural collective resilience with citizens from their host country. Overall, this study emphasized the significance of host country members who can promote certain coping mechanisms for their visitors in the specific regional and geographical context of China.

An Esthetic Evaluation of Different Abutment Materials in the Anterior Maxilla: A Randomized Controlled Clinical Trial Using a Crossover Design.

PURPOSE: To assess the effect of implant abutment material and soft tissue thickness on the peri-implant soft tissue color using spectrophotometry and to evaluate gingival esthetics and patient satisfaction with three different abutments. MATERIALS AND METHODS: Twenty-five patients with a missing maxillary tooth in the esthetic area received an endosseous implant using a two-stage protocol. Gray titanium, pink anodized titanium, and hybrid zirconia custom abutments were fabricated for each participant and inserted for one week with a cross-over design in a randomized manner. Color measurements were made using a spectrophotometer comparing midfacial peri-implant soft tissue and marginal gingiva of the contralateral tooth. CIE Lab color scale was used following the formula: ΔE = [(∆L)2 + (∆a)2 + (∆b)2 ]½ . PES scores were recorded, and patient satisfaction questionnaires were completed at each abutment change visit and at 1-year follow-up. Statistical analysis was performed using Friedman's test and the Wilcoxon signed-rank test with Bonferroni correction as well as the Mann-Whitney U test (α = 0.05). RESULTS: Abutment material type significantly affected the ΔΕ values of the peri-implant mucosa when compared to the contralateral teeth. At baseline, the highest ΔΕ means ± standard deviation (SD) values were obtained with gray titanium (11.25 ± 2.98), followed by pink anodized titanium (9.90 ± 2.51), and zirconia abutments (6.46 ± 1.43). Differences were statistically significant irrespective of soft tissue thickness. The highest PES values were obtained with zirconia abutments (10.88 ± 0.88), followed by pink anodized titanium (10.12 ± 1.13) and the lowest with gray titanium (9.68 ± 1.41). PES differences were significant only for the thin soft tissue group. Regarding patient satisfaction, VAS scores for the pink anodized and zirconia hybrid abutment groups were higher than the gray titanium group for each question. CONCLUSION: The color difference between soft tissues around teeth and implants was significant in all groups regardless of tissue thickness. The hybrid zirconia abutments resulted in the least color difference, followed by pink anodized and gray titanium. Significantly different PES values were recorded only for the thin tissue group. There was no significant difference in patient satisfaction between zirconia and pink anodized abutments at the 1-year follow up. Pink anodized abutments represent a good esthetic alternative to zirconia hybrid abutments especially in mechanically challenging situations.

Digital Workflow for Double Complete Arch Zirconia Prostheses Utilizing a Novel Scan Body.

The purpose of this clinical report is to present a complete digital workflow for the fabrication of complete arch fixed zirconia implant restorations. An intraoral scanner was used to capture the implants' position at the abutment level and also the patient's existing interim prostheses with the double digital scanning technique. A novel scan body and impression pin were utilized throughout the scanning process which allowed for the accurate and reproducible superimposition of the generated Standard Tesselation Language (STL) files. Prosthesis prototypes were digitally designed and fabricated, tried in, and verified intraorally. The definitive zirconia prostheses were then fabricated and delivered to the patient. This technique can be utilized in both arches overcoming the absence of stable intraoral landmarks for superimposition of STL files.

Estimands in hematologic oncology trials.

The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a crucial role in determining the strategy and defining the estimand for clinical trial designs. Clinical trials in patients with hematological malignancies often present unique challenges for trial design due to complexity of treatment options and existence of potential curative but highly risky procedures, for example, stem cell transplant or treatment sequence across different phases (induction, consolidation, maintenance). Here, we illustrate how to apply the estimand framework in hematological clinical trials and how the estimand framework can address potential difficulties in trial result interpretation. This paper is a result of a cross-industry collaboration to connect the International Conference on Harmonisation (ICH) E9 addendum concepts to applications. Three randomized phase 3 trials will be used to consider common challenges including intercurrent events in hematologic oncology trials to illustrate different scientific questions and the consequences of the estimand choice for trial design, data collection, analysis, and interpretation. Template language for describing estimand in both study protocols and statistical analysis plans is suggested for statisticians' reference.

The da1 mutation in wheat increases grain size under ambient and elevated CO2 but not grain yield due to trade-off between grain size and grain number.

Grain size is potentially yield determining in wheat, controlled by the ubiquitin pathway and negatively regulated by ubiquitin receptor DA1. We analyzed whether increased thousand grain weight in wheat da1 mutant is translated into higher grain yield and whether additional carbon provided by elevated (e)CO2 can be better used by the da1, displaying higher grain sink strength and size. Yield-related, biomass, grain quality traits, and grain dimensions were analyzed by two-factorial mixed-model analysis, regarding genotype and eCO2. da1 increased grain size but reduced spikes and grains per plant, grains per spike, and spikelets per spike, independent of eCO2 treatment, leaving total grain yield unchanged. eCO2 increased yield and grain number additively and independently of da1 but did not overcome the trade-off between grain size and number observed for da1. eCO2 but not da1 impaired grain quality, strongly decreasing concentrations of several macroelement and microelement. In conclusion, intrinsic stimulation of grain sink strength and grain size, achieved by da1, is not benefitting total yield unless trade-offs between grain size and numbers can be overcome. The results reveal interactions of yield components in da1-wheat under ambient and eCO2, thereby uncovering limitations enhancing wheat yield potential.

Comparative analysis of dimensional alterations following extraction of maxillary molars using three-dimensional images' superimposition: a CBCT study.

The aims of this study were to (i) evaluate the bone alterations following maxillary molar extraction and (ii) identify the factors associated with bone alterations using a tomographic analysis. Cone Beam Computer Tomographies (CBCTs) of 17 subjects with 25 maxillary molars were analyzed, before and, in average, 12 months following extraction. Fifty CBCTs were segmented as 3D models that were used as reference for analysis. Cross-sectional planes were established to measure the dimensional changes in the vertical, horizontal aspects, and the area of the alveolar bone. Associations between root divergence, initial bone location related to the maxillary sinus, and the thickness of buccal and palatal bone at baseline was assessed using mixed-effect models. Overall, the average reduction in vertical bone height was 35.23% (2.61 ± 1.76 mm). The mean reduction of area of alveolar process and horizontal bone width were 18.89% (56.08 ± 44.23 mm2) and 65.10% (8.33 ± 4.51 mm), respectively. There was a marginal significant association between horizontal bone changes and the thickness of palatal bone (p = 0.05). The results of the present study indicated that following maxillary molar extraction, significant dimensional changes occur in both the vertical and horizontal directions. The vertical changes were mainly attributed to remodeling on the coronal aspect of the alveolar ridge and sinus pneumatization was rare.

Accuracy of Guided Implant Surgery in 25 Edentulous Arches: A Laboratory Observational Study.

PURPOSE: To assess the accuracy of template-guided implant surgery for edentulous arches. MATERIALS AND METHODS: The stone master casts of 25 edentulous arches treated with either 4 or 6 implants with CBCT generated template-guided surgery were included in this observational cohort study. The stone casts generated from the surgical templates (group one) prior to implant placement were digitized into Standard Tesselation (STL) files with a reference scanner. For comparison, the stone master casts derived from intraoral complete-arch impressions after implant placement (group two) were also digitized. The resultant STL files were superimposed and best-fit-alignment algorithm was used to quantify the 3D deviations present between the two groups. Descriptive statistics were computed for all categorical variables. Due to the presence of nonindependent samples between maxillary and mandibular casts, a mixed-effects model was used. RESULTS: Deviations between the implant analogs of the stone casts representing digitally planned versus actually placed implants were found. The mean root-mean-square error (RMSE) between all 25 arches was found to be 0.2 mm (SD ± 0.15). The mean RMSE between presurgical and postsurgical maxillary stone casts were 0.19 ± 0.15 mm, while between mandibular stone casts were 0.21 ± 0.16 mm and were not significant (p = 0.67). The mean RMSE between presurgical and postsurgical stone casts arches with 4 versus 6 implants were found to be significant (p = 0.01). CONCLUSIONS: According to the results of the study and based on the amount of 3D deviations between the digitally planned implant positions and the actually placed implants, template-guided surgery is a safe treatment modality for implant placement in edentulous arches.

Wheat (Triticum aestivum L.) Breeding from 1891 to 2010 Contributed to Increasing Yield and Glutenin Contents but Decreasing Protein and Gliadin Contents.

Epidemiologic studies suggest an increasing prevalence of celiac disease and non-celiac gluten/wheat sensitivity. With wheat proteins being the main triggers, changes in wheat protein composition are discussed as a potential cause. The goals of breeding toward increased yield and resistance might have inadvertently contributed to a higher immunostimulatory potential of modern wheat cultivars compared to old wheat cultivars. Therefore, agronomic characteristics, protein content, and gluten composition of 60 German winter wheat cultivars first registered between 1891 and 2010 grown in 3 years were analyzed. While plant height and spike density decreased over time, yield and harvest index increased. The protein and gliadin contents showed a decreasing trend, whereas glutenin contents increased, but there were no changes in albumin/globulin and gluten contents. Overall, the harvest year had a more significant effect on protein composition than the cultivar. At the protein level, we found no evidence to support an increased immunostimulatory potential of modern winter wheat.

Barley HISTIDINE KINASE 1 (HvHK1) coordinates transfer cell specification in the young endosperm.

Cereal endosperm represents the most important source of the world's food; nevertheless, the molecular mechanisms underlying cell and tissue differentiation in cereal grains remain poorly understood. Endosperm cellularization commences at the maternal-filial intersection of grains and generates endosperm transfer cells (ETCs), a cell type with a prominent anatomy optimized for efficient nutrient transport. Barley HISTIDINE KINASE1 (HvHK1) was identified as a receptor component with spatially restricted expression in the syncytial endosperm where ETCs emerge. Here, we demonstrate its function in ETC fate acquisition using RNA interference-mediated downregulation of HvHK1. Repression of HvHK1 impairs cell specification in the central ETC region and the development of transfer cell morphology, and consecutively defects differentiation of adjacent endosperm tissues. Coinciding with reduced expression of HvHK1, disturbed cell plate formation and fusion were observed at the initiation of endosperm cellularization, revealing that HvHK1 triggers initial cytokinesis of ETCs. Cell-type-specific RNA sequencing confirmed loss of transfer cell identity, compromised cell wall biogenesis and reduced transport capacities in aberrant cells and elucidated two-component signaling and hormone pathways that are mediated by HvHK1. Gene regulatory network modeling was used to specify the direct targets of HvHK1; this predicted non-canonical auxin signaling elements as the main regulatory links governing cellularization of ETCs, potentially through interaction with type-B response regulators. This work provides clues to previously unknown molecular mechanisms directing ETC specification, a process with fundamental impact on grain yield in cereals.

Digital Workflow for Implant Rehabilitation with Double Full-Arch Monolithic Zirconia Prostheses.

The purpose of the present report is to illustrate a proof-of-concept protocol with the double digital scanning (DDS) technique for complete digital workflow in double full-arch implant rehabilitation. Two patients (4 restored arches) presented with hopeless dentitions and they were treated with a 4-appointment prosthodontic protocol and monolithic zirconia prostheses implementing a complete digital workflow. The outcomes are presented after clinical and radiographic observation for 2 years.

Digital workflow: In vitro accuracy of 3D printed casts generated from complete-arch digital implant scans.

STATEMENT OF PROBLEM: Data on the accuracy of printed casts from complete-arch digital implant scans are lacking. PURPOSE: The purpose of this in vitro study was to compare the 3D accuracy of printed casts from a complete-arch digital implant intraoral scan with stone casts from conventional impressions. MATERIAL AND METHODS: An edentulous mandibular cast with 4 multiunit abutments with adequate anteroposterior spread was used as the master cast. Digital scans (n=25) were made by using a white light intraoral scanner (IOS). The generated standard tessellation language (STL) data sets were imported into a computer-assisted design (CAD) software program to generate complete-arch implant casts through 3D printing technology. The 25 printed casts and the mandibular master cast were further digitized by using a laboratory reference scanner (Activity 880; Smart Optics). These STL data sets were superimposed on the digitized master cast in a metrology software program (Geomagic Control X) for virtual analysis. The root mean square (RMS) error and the average offset were measured. RESULTS: When compared with the master cast, the printed casts had a mean ±standard deviation RMS error of 59 ±16 µm (95% CI: 53, 66). The maximum RMS error reached 98 µm. The average offsets were all negative, with a significant difference compared with zero (P<.001). CONCLUSIONS: The implant 3D deviations of the printed casts from complete-arch digital scans had statistically significant differences compared with those of the master cast but may still be within the acceptable range for clinical application.

Effect of time in function on the predictability of short dental implants (≤6 mm): A meta-analysis.

PURPOSE: To analyse randomised controlled clinical trials (RCTs) and prospective cohort studies reporting on the survival and failure rates of functionally loaded short implants (SI) based on the actual length of time in function. MATERIALS AND METHODS: This meta-analysis was conducted according to PRISMA guidelines for systematic reviews. Electronic and manual searches were conducted to identify RCTs and prospective cohort studies reporting survival and complication rates of short dental implants (≤6 mm) based on the time in function. Secondary outcomes included the location (maxilla or mandible), type of restoration (single crown [SC] versus fixed dental prosthesis [FDP]) and marginal bone loss (MBL). RESULTS: A total of 20 studies (11 RCTs and 9 prospective) fulfilled the inclusion criteria and featured a total of 1238 SI placed in 747 patients. The overall (early and late) mean percentage of short implant failure was 4%. SI with up to 1-year follow-up presented failure rate of 2%, while SI followed up for >3 years showed a failure rate of 10%. SI restored with SC presented a late failure rate of 4% while SI restored with FPD 2%. The late failure rate did not differ in terms of location (maxilla or mandible) both with 3%. CONCLUSION: Short implants in function for more than 3 years presented higher failure rates compared to SI in function for <3 years. Splinting crowns supported by SIs in the posterior area should be considered. However, SI is a valid option for selected cases given their relatively high long-term survival rates.

Technical Complications and Prosthesis Survival Rates with Implant-Supported Fixed Complete Dental Prostheses: A Retrospective Study with 1- to 12-Year Follow-Up.

PURPOSE: To report the rate of technical complications and prosthesis survival in a cohort of edentulous patients treated with implant-supported fixed complete dental prostheses (IFCDPs) after a mean observation period of at least 1 year. MATERIALS AND METHODS: The single-visit examination included clinical and radiographic assessment, occlusal analysis, photographs and questionnaire assessing patient satisfaction in a cohort of 52 patients rehabilitated with 71 IFCDPs (supported by 457 implants). The IFCDPs were assessed for technical complications, number of implants and cantilever extension, retention type and prosthetic material type. Comparison was made between ceramic IFCDPs (Group 1) and metal-resin IFCDPs (Group 2). Kaplan-Meier survival curve analysis was carried out for assessment of prosthesis survival and was done for both Groups 1 and 2 separately. The Cox proportional hazard model was used for survival analysis, adjusting for a number of potential confounders, to evaluate the association between prosthesis survival and several risk factors such as type of opposing occlusion, nightguard use, and presence of bruxism. Responses to patient satisfaction questions were compared with Fisher's exact test. RESULTS: Out of 71 edentulous arches (52 patients) restored with IFCDPs, 6 IFCDPs had failed, yielding a cumulative prosthesis survival rate of 91.6 % after a mean observation period of 5.2 years (range: 1-12 years) after definitive prosthesis insertion. Three IFCDPs were lost due to implant failures after 5.8 to 11 years of functional loading. Additionally, 3 metal-resin IFCDPs failed due to technical complications. Minor complications were the most frequent complications observed, namely wear of the prosthetic material (9.8% annual rate) being the most common, followed by decementation of cement-retained IFCDPs (2.9%), and loss of the screw access filing material of the screw-retained IFCDPs (2.7%). The most frequently observed major complication was fracture of the prosthetic material (1.9% annual rate), followed by fracture of occlusal screw (0.3%), and fracture of framework (0.3%). The annual rate of wear of prosthetic material was 7.3% for porcelain IFCDPs (n = 19/55) and 19.4% for metal-resin IFCDPs (n = 13/16), yielding a statistically significant difference between the 2 groups (p = 0.01). CONCLUSIONS: After a mean exposure time of 5.2 years, 91.6% prosthesis survival rates were achieved (65 out of 71 IFCDPs). The most frequent minor technical complication was wear of the prosthetic material with estimated 5-year rate of 49.0%, while the most frequent major complication was fracture of the prosthetic material with estimated 5-year dental unit-based rate of 9.5%. The cumulative rates for "prosthesis free of minor complications" at 5- and 10-years were 60.5% (95% CI: 47.2-71.3%) and 8.9% (95% CI: 2.9-18.0%), respectively. The cumulative rates for "prosthesis free of major technical complications" at 5- and 10-years were 85.5% (95% CI: 73.0-92.5%) and 30.1% (95% CI: 12.0-50.6%), respectively. Presence of bruxism, and absence of a nightguard were associated with increased risk for chipping of the prosthetic material of the IFCDPs.