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- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Semb, Gunvor, et al.
(författare)
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A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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| 3. |
- Alissa, Rami, et al.
(författare)
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Einfluss von Ibuprofen auf die Knochenheilung an Dentalimplantaten Eine randomisierte klinische Doppelblindstudie mit Plazebokontrolle : Effect of Ibuprofen of the bone cure in case of dental implants A random clinical double blind, placebo-controlled study
- 2010
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Ingår i: IMPLANTOLOGIE. - 0943-9692. ; 18:1, s. 61-76
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Tidskriftsartikel (refereegranskat)abstract
- Diese randomisierte plazebokontrollierte Doppelblindstudie wurde durchgeführt, um den Einfluss postoperativer Gaben von 600 mg Ibuprofen (eine Woche lang viermal täglich) auf das marginale Knochenniveau rund um Dentalimplantate zu untersuchen. Insgesamt wurden 61 Patienten entweder der Ibuprofen-Gruppe (n = 31) oder der Plazebo-Gruppe (n = 30) zugeordnet. Von 132 eingesetzten Implantaten entfielen 67 auf die Ibuprofen-Gruppe und 65 auf die Plazebo-Gruppe. Die Präparation der Implantatstollen erfolgte per intermittierender Bohrabfolge, angepasst an die Implantatdurchmesser und die lokale Knochenqualität entsprechend den Implantationsrichtlinien von Astra Tech. Untersucht wurden in erster Linie die Veränderungen des marginalen Knochenniveaus an den Dentalimplantaten vom Ausgangspunkt zwei Wochen nach der Implantation bis zu den Röntgenuntersuchungen nach drei und sechs Monaten. Die Zahnfilme wurden in Paralleltechnik unter Verwendung eines Filmhalters mit Strahlenleitvorrichtung aufgenommen. Mit Sichtbox und Handlupe (Vergrößerungsfaktor 8) wurde gemessen, wie stark sich das Knochenniveau veränderte. Zwei Patienten aus der Ibuprofen-Gruppe konnten die verordnete Anwendung des Medikaments wegen einer geringfügigen subjektiven Magenverstimmung nicht zu Ende führen. In der Kontrollgruppe erschien ein Patient zu keinem einzigen der vereinbarten Termine nach den Implantationen. Somit gab es insgesamt drei Studienabbrecher. Während der sechsmonatigen Beobachtungsdauer blieben alle Implantate in beiden Gruppen intakt. In der Ibuprofen-Gruppe reduzierten sich die Ausgangswerte beim Knochenniveau nach drei Monaten um durchschnittlich 0,33 mm und nach sechs Monaten um 0,29 mm. In der Plazebo-Gruppe waren diese Werte um 0,12 mm beziehungsweise 0,30 mm reduziert. Signifikante Gruppenunterschiede beim mittleren marginalen Knochenniveau zeigten sich weder nach drei (p = 0,27) noch nach sechs Monaten (p = 0,97). Es wurde geschlussfolgert, dass kurzfristige systemische Schmerzbehandlungen mit Ibuprofen in der frühen Einheilphase von Implantaten offenbar keinen signifikanten Einfluss auf den marginalen Knochen an Dentalimplantaten haben.
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| 6. |
- Esposito, Marco, 1965, et al.
(författare)
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Does antibiotic prophylaxis at implant placement decrease early implant failures? A Cochrane systematic review.
- 2010
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Ingår i: European journal of oral implantology. - 1756-2406. ; 3:2, s. 101-10
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Tidskriftsartikel (refereegranskat)abstract
- Marco Esposito is the first author of two of the included studies; however, he was not involved in the quality assessment of these trials. This review is based on a Cochrane systematic review entitled 'Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications' published in The Cochrane Library (see http://www.cochrane.org for more information). Cochrane systematic reviews are regularly updated to include new research, and in response to comments and criticisms from readers. If you wish to comment on this review, please send your comments to the Cochrane website or to Marco Esposito. The Cochrane Library should be consulted for the most recent version of the review. The results of a Cochrane Review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of the review authors, and are not necessarily shared by the Cochrane Collaboration.To assess the beneficial or harmful effects of systemic prophylactic antibiotics at dental implant placement versus no antibiotic/placebo administration and, if antibiotics are of benefit, to find which type, dosage and duration is the most effective.The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched up to 2 June 2010 for randomised controlled clinical trials (RCTs) with a follow-up of at least 3 months comparing the administration of various prophylactic antibiotic regimens versus no antibiotics to patients undergoing dental implant placement. Outcome measures were prosthesis failures, implant failures, postoperative infections and adverse events (gastrointestinal, hypersensitivity, etc.). Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Meta-analyses were conducted.Four RCTs were identified: three comparing 2 g of preoperative amoxicillin versus placebo (927 patients) and the other comparing 1 g of preoperative amoxicillin plus 500 mg four times a day for 2 days versus no antibiotics (80 patients). The meta-analyses of the four trials showed a statistically significantly higher number of patients experiencing implant failures in the group not receiving antibiotics: risk ratio=0.40 (95% confidence interval (CI) 0.19 to 0.84). The number needed to treat (NNT) to prevent one patient having an implant failure is 33 (95% CI 17-100), based on a patient implant failure rate of 5% in patients not receiving antibiotics. The other outcomes were not statistically significant, and only two minor adverse events were recorded, one in the placebo group.There is some evidence suggesting that 2 g of amoxicillin given orally 1 h preoperatively significantly reduce failures of dental implants placed in ordinary conditions. No significant adverse events were reported. It might be sensible to suggest the use of a single dose of 2 g prophylactic amoxicillin prior to dental implant placement. It is still unknown whether post-operative antibiotics are beneficial, and which is the most effective antibiotic.
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