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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 4. |
- Esposito, Marco, 1965, et al.
(författare)
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Immediately loaded zygomatic implants vs conventional dental implants in augmented atrophic maxillae: 4 months post-loading results from a multicentre randomised controlled trial
- 2018
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Ingår i: European Journal of Oral Implantology. - 1756-2406. ; 11:1, s. 11-28
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare the clinical outcome of immediately loaded cross-arch maxillary prostheses supported by zygomatic implants vs conventional implants placed in augmented bone. Materials and methods: A total of 71 edentulous patients with severely atrophic maxillas, who did not have sufficient bone volume to place dental implants or when it was possible to place only two implants in the front area (minimal diameter 3.5 mm and length of 8 mm) and less than 4.0 mm of bone height subantrally, were randomised according to a parallel group design. They (35 patients) received zygomatic implants to be loaded immediately vs grafting with a xenograft, followed, after 6 months of graft consolidation, by the placement of six to eight conventional dental implants, submerged for 4 months (36 patients). To be loaded immediately, zygomatic implants had to be inserted with an insertion torque superior to 40 Ncm. Screw-retained, metal-reinforced, acrylic provisional prostheses were provided to be replaced by definitive Procera Implant Bridge Titanium prostheses (Nobel Biocare, Göteborg, Sweden) with ceramic or acrylic veneer materials 4 months after initial loading. Outcome measures were: prosthesis, implant and augmentation failures, any complications, quality of life (OHIP-14), the number of days that patients experienced total or partial impaired activity, time to function, and number of dental visits, assessed by independent assessors. Patients were followed up to 4 months after loading. Results: No augmentation procedure failed. Three patients dropped out from the augmentation group. Six prostheses could not be delivered or failed in the augmentation group vs one prosthesis in the zygomatic group, the difference being statistically significant (difference in proportions = 15.32%; P = 0.04; 95% CI: 0.23 to 31.7). Eight patients lost 35 implants in the augmentation group vs three implants in one patient from the zygomatic group, the difference being statistically significant (difference in proportions = 21.38%; P = 0.001; 95% CI: 3.53 to 39.61). In total, 14 augmented patients were affected by 20 complications vs 26 zygomatic patients (35 complications), the difference being statistically significant (difference in proportions = 31.87%; P = 0.008; 95% CI: 6.48 to 53.37). The OHIP-14 score was 3.68 ± 5.41 for augmented patients and 4.97 ± 5.79 for zygomatic patients, with no statistically significant differences between groups (mean difference = 1.29; 95%CI -1.60 to 4.18; P = 0.439). Both groups had significantly improved OHIP-14 scores from before rehabilitation (P < 0.001 for both augmented and zygomatic patients). The number of days of total infirmity was, on average, 7.42 ± 3.17 for the augmented group and 7.17 ± 1.96 for the zygomatic group, the difference not being statistically significant (mean difference = -0.25; 95% CI: -1.52 to 1.02; P = 0.692). Days of partial infirmity were on average 14.24 ± 4.64 for the augmented group and 12.17 ± 3.82 for the zygomatic group, the difference being statistically significant (mean difference = -2.07; 95% CI: -4.12 to -0.02; P = 0.048). The mean number of days to have a functional prosthesis was 444.32 ± 207.86 for augmented patients and 1.34 ± 2.27 for zygomatic patients, the difference being statistically significant (mean difference = -442.9; 95% CI: -513.10 to -372.86; P < 0.001). The average number of dental visits was 16.79 ± 10.88 for augmented patients and 12.58 ± 5.21 for zygomatic patients, the difference not being statistically significant (mean difference = -4.21; 95% CI -8.48 to 0.06; P = 0.053). Conclusions: Preliminary 4-months post-loading data suggest zygomatic implants were associated with statistically significantly less prosthetic (one vs six patients) and implant failures (one patient lost three implants versus 35 implants in eight patients) as well as time needed to functional loading (1.3 days vs 444.3 days) when compared with augmentation procedures and conventionally loaded dental implants. Even if more complications were reported for zygomatic imp ants, which were solved spontaneously or could be handled, zygomatic implants proved to be a better rehabilitation modality for severely atrophic maxillae. Long-term data are essential to confirm or dispute these preliminary results. Conflict of interest statement: This study was originally supported by Nobel Biocare, the manufacturer of the implants, and the provisional and definitive prosthetic components used in this study, which were provided free for the patients. However, before any results were known, Nobel Biocare withdrew the financial support and recruitment had to be stopped. Tecnoss (Giaveno, Torino, Italy) kindly donated the bone substitutes and the membranes, whereas Global D (Brignais, France) donated the osteosynthesis screws. Data property belonged to the authors and by no means did the manufacturers interfere with the publication of the results. © 2002-2018 Quintessence Publishing Group.
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