A randomized clinical trial on zirconia versus titanium implants in maxillary single tooth replacement.

OBJECTIVES: This RCT aimed to compare zirconia and titanium dental implants in the maxillary premolar region. The comparison was based on marginal bone level (MBL) changes, clinical parameters, aesthetic outcomes, and patient related outcome measures (PROMs) 1 year after prosthetic loading. MATERIALS AND METHODS: Fifty patients were randomly assigned to receive either a zirconia (ZrO2, n = 25) implant or a titanium (Ti, n = 25) bone-level implant. Implants were provided with a lithium disilicate crown 3 months after placement. Follow-up was at 1 month and after 1 year. The primary outcome pertained to changes in MBL. Reported secondary outcomes consisted of implant survival, peri-implant tissue health, aesthetics, and PROMs. RESULTS: Mean MBL change after 1 year was 0.01 mm (SD = 0.45; min = 0.72, max = 0.86) for ZrO2 and -0.09 mm (SD = 0.34; min = 0.53, max = -1.06) for Ti (p = .439). Scores for the other clinical outcome parameters and PROMs were generally favorable, with no significant differences. However, significant differences were found for the aesthetic outcomes regarding two criteria: (a) level of facial mucosa (p = .022), in favor of Ti, and (b) root convexity/soft tissue color and texture (p = .005) in favor of ZrO2. CONCLUSION AND CLINICAL IMPLICATIONS: The ZrO2 and Ti implant types used in this study, replacing a single missing maxillary premolar, show a comparable outcome in terms of MBL change after 1 year. Clinical and aesthetic parameters, as well as PROMs, are favorable and similar between both implant types after 1 year of prosthetic loading. These short-term study results suggest that both are suitable for clinical use.

Dimensional changes of CAD/CAM polymer crowns after water aging - An in vitro experiment.

Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM) polymers can potentially replace traditional materials used for manufacturing indirect restorations. In 2012, Lava Ultimate (LU) was introduced as a highly suitable material for implant-supported single crowns. Three years after its introduction, the manufacturer issued a change in indication for the material, implying that they no longer considered the material to be suitable for crown indications due to debonding issues. A clinical trial with implant-borne Lava Ultimate crowns bonded to zirconia abutments revealed that 80 percent of the LU crowns showed debonding from the abutment within one year, whereas no debonding occurred when an alternative full-ceramic restoration material was used. These results suggest that the material itself had been the cause of the debonding. However, the exact reason for the debonding remained unclear. Water uptake in resin methacrylates like LU is known to cause dimensional changes resulting in mechanical stress on the RelyX Ultimate (RU) cement. The purpose of this study is to quantify the dimensional changes in LU caused by water uptake and relate these dimensional changes to the failure of the RU cement. Twenty-five identical LU-crowns were divided into three groups. 10 LU-crowns with abutment and 10 crowns without abutments were stored in water for 23 days and were only removed for measurement. Five crowns served as a control to calibrate the measurements. The internal diameter was measured eight times with a TS 460 Heidenhain touch probe. For visualization purposes, one crown was also 3D scanned before and after water treatment. The results showed that after 23 days in water the mean increase in diameter for the groups with and without abutment was 36.6 µm (SD = 35,1) and 36.7 µm (SD = 26,5) respectively. Mixed effects modelling indicated no significant between-group differences at any time point. Exposure of LU to water results in dimensional changes causing mechanical stress on the crown-abutment complex. It can be estimated that RU cement fails after an expansion of more than 4 µm. Within the limitations of this in vitro study, it can be concluded that the dimensional changes induced by water uptake can cause debonding issues. As more CAD/CAM polymers for restorative purposes are expected to be developed, the results of this study should stimulate manufacturers to quantify their products' dimensional changes in a wet environment before market release.

Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study.

BACKGROUND: Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality. METHODS: Participants (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality. RESULTS: The mean protein-adjusted serum free thiol level was 5.05 ± 1.02 µmol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio [HR] per doubling 0.68 [95% confidence interval [CI] 0.47-1.00], P = 0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 [95% CI 0.44-1.00], P = 0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria. CONCLUSIONS: In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.

Asthma in 9-year-old children of subfertile couples is not associated with in vitro fertilization procedures.

Asthma is a chronic reversible obstructive airway disease, which is common among children and leads to respiratory impairment. Studies showed that asthma is more common among children born after in vitro fertilization (IVF) than among spontaneously conceived children. However, it is unknown which component of the IVF procedure contributes to this putative link. Therefore, the aim of this prospective follow-up study was to differentiate the possible effect of ovarian hyperstimulation from that of the in vitro culture procedure on asthma and rhinitis in 9-year-old children conceived with IVF. The study comprised three groups of singletons: (I) conceived with ovarian hyperstimulation-IVF (COH-IVF, n = 95); (II) conceived with modified natural cycle-IVF (MNC-IVF, n = 48); and (III) naturally conceived to subfertile couples (Sub-NC, n = 68). Parents filled out the validated Dutch version of the asthma questionnaire of the International Study of Asthma and Allergies. Asthma prevalence in the groups did not differ: COH-IVF n = 8 (8%); MNC-IVF n = 0 (0%); and Sub-NC n = 4 (6%). Adjustment for confounders did not alter the results.Conclusion: Neither ovarian hyperstimulation nor the in vitro culture procedure was associated with asthma and rhinitis at 9 years. IVF children had a similar prevalence of asthma compared with children conceived naturally by subfertile couples.Trial registration: ISRCTN76355836 What is Known: • An increased risk for asthma has been observed in children born after in vitro fertilization at preschool and school age. • The association between IVF and asthma may be partly explained by parental subfertility. What is New: • IVF children do not have a higher prevalence of asthma than children of subfertile couples conceived naturally. • Ovarian hyperstimulation used in IVF is not associated with asthma in 9-year-old children of subfertile couples.

Increased time to pregnancy is associated with less optimal neurological condition in 4-year-old singletons, in vitro fertilization itself is not.

STUDY QUESTION: Does ovarian hyperstimulation, the in vitro procedures required for in vitro fertilization (IVF)/ intracytoplasmic sperm injection or the combination of both, affect the neurological outcome of 4-year-old singletons? SUMMARY ANSWER: Ovarian hyperstimulation, the in vitro procedure and the combination of both, were not associated with the worse neurological outcome in 4-year-old singletons. WHAT IS KNOWN ALREADY: Assisted reproduction techniques (ARTs) are not associated with neurological dysfunction during the first post-natal years; however, effects on the long-term neurological outcome are still inconclusive. An increased time to pregnancy (TTP, a proxy for the severity of subfertility) has been associated with a less optimal neurological condition at age 2. The present study focuses on the neurodevelopmental outcome of 4-year-old ART-offspring. STUDY DESIGN, SIZE, DURATION: Longitudinal, prospective follow-up study. PARTICIPANTS, SETTING, METHODS: Four-year-old singletons born to subfertile parents (subfertile group, n = 195), including singletons born after controlled ovarian hyperstimulation IVF (COH-IVF, n = 63), modified natural cycle IVF (MNC-IVF, n = 53) and natural conception (Sub-NC, n = 79). Data on underlying cause of subfertility and TTP were present. In addition, we assessed newly recruited 4-year-old singletons born to fertile parents after natural conception (reference group, n = 98). Neurological development was evaluated with the neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the occurrence of the clinically relevant form of minor neurological dysfunction (complex MND). The primary outcome was the fluency score, as fluency of movements is easily reduced by subtle brain dysfunction. Data were analysed with univariable and multivariable regression analyses, in which special attention was paid to sex differences in the neurological outcome. MAIN RESULTS AND THE ROLE OF CHANCE: The fluency score, NOS and the prevalence of complex MND were similar in COH-IVF, MNC-IVF and Sub-NC children. The neurological condition of children born to subfertile parents was similar to that of children of fertile parents and was independent of the underlying cause of subfertility. No statistically significant associations were found between TTP and the fluency score and NOS. However, a positive correlation was found between TTP and the prevalence of complex MND (TTP in years, adjusted odds ratio [OR] [95% confidence interval, CI]: 1.207 [1.038 to 1.404], P = 0.014); a correlation which could be attributed to girls, in whom an evident positive correlation was present (adjusted OR [95% CI]: 1.542 [1.161 to 2.047], P = 0.003). A similar association was absent in boys. LIMITATIONS, REASONS FOR CAUTION: The prospective design of our study and small post-natal attrition rate (9.3%) reduced potential selection bias based on the child's development or health. The assessors were blind to the mode of conception, except for the group of children born to fertile parents, which was newly recruited. The study lacks sufficient power to conclude firmly that increased TTP is associated with a higher prevalence of complex MND. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that the severity of subfertility, rather than its simple presence or components of IVF treatment, affects the neurological outcome. Moreover, girls may be neurologically more vulnerable for the effect of severity of subfertility. The finding that the severity of subfertility may be the decisive factor rather than the presence of a history of subfertility per se corroborates previous reports. Our results cannot be generalized to multiples, as we studied singletons only. STUDY FUNDING/COMPETING INTERESTS: The study was financially supported by the University Medical Center Groningen, grant number: 754510, the Junior Scientific Masterclass, the Postgraduate School Behavioural and Cognitive Neurosciences and the Cornelia Foundation, Groningen, The Netherlands. The authors have no conflicts of interest to declare.

The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT.

STUDY QUESTION: Does embryo biopsy inherent to preimplantation genetic screening (PGS) affect neurological, cognitive and behavioural development of 4-year-old children? SUMMARY ANSWER: PGS does not seem to affect neurological, cognitive and behavioural development of 4-year-old singletons; however, our data suggest that it may be associated with altered neurodevelopment in twins. WHAT IS KNOWN ALREADY: Evidence concerning the safety of PGS on neurodevelopmental outcome in offspring is scarce. The present study provides information on neurodevelopmental, cognitive and behavioural outcome of 4-year-old PGS offspring. STUDY DESIGN, SIZE, DURATION: A prospective, assessor-blinded follow-up study of children born to women who participated in a multi-centre RCT on the effect of IVF with or without PGS. PARTICIPANTS/MATERIALS, SETTING, METHODS: At 4 years, 49 children (31 singletons, 9 sets of twins) born following IVF with PGS and 64 children (42 singletons, 11 sets of twins) born following IVF without PGS (controls) were assessed (post-natal attrition 18%). Neurological development was evaluated with the standardized, age-specific and sensitive neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the rate of adverse neurological outcome. Primary outcome was the fluency score, as fluency of movements is easily reduced by subtle dysfunction of the brain. Cognitive development was evaluated with the Kaufman Assessment Battery for Children; behavioural development was evaluated with the Child Behavior Checklist. The effect of PGS was analysed with a mixed effects model. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the intention to treat analysis, neurodevelopmental outcome of PGS children was similar to that of controls. However, additional analyses indicated that PGS affected neurodevelopmental outcome of twins in a different way than that of singletons. The fluency score of singletons born following PGS was similar to that of control singletons [mean values, 95% confidence intervals (CIs): 12.2 (11.5;12.8) and 12.2 (11.6;12.8)], respectively, P = 0.977) that was also true for the other neurodevelopmental parameters. The fluency score of PGS twins was significantly lower than that of control twins [mean values, 95% CIs: 10.6 (9.8;11.3) and 12.3 (11.5;13.1)], respectively, P = 0.001); the same was true for the NOS. In addition, PGS in twins was associated with a higher sequential intelligence quotient score. On the other hand, other neurodevelopmental parameters were similar for PGS twins and control twins. Post hoc sample size calculation for the primary outcome parameter, the fluency score, indicated that the study groups, including the subgroups of singletons and twins, were adequately powered. LIMITATIONS, REASONS FOR CAUTION: We assessed singletons and twins who contributed to the generalizability of the study. A limitation of our study is the relative small size of our study groups and the selective dropout in both groups (dropouts PGS group: higher gestational age; control group: less well-educated parents). These preclude the conclusion that PGS per se is not associated with neurodevelopmental, cognitive and behavioural problems in singletons and the conclusion that PGS is associated with altered neurodevelopmental outcome in twins. WIDER IMPLICATIONS OF THE FINDINGS: The need for careful long-term monitoring of children born following embryo biopsy remains, as it is still applied in the form of PGD and it is still unknown whether embryo biopsy affects long-term neurodevelopmental outcome.