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- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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- Mylrea-Foley, Bronacha, et al.
(författare)
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Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction
- 2023
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Ingår i: Ultraschall in der Medizin. - : Georg Thieme Verlag KG. - 0172-4614. ; 44:1, s. 56-67
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). Materials and Methods A prospective European multicenter observational study included women with a singleton pregnancy, 32 +0-36 +6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] <10 th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of >40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (<0.9) or abnormal (≥0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. Results 856 women had 2770 measurements; 696 (81%) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7%) a UCR ≥0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30% vs. 9%, relative risk 3.2; 95%CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67% (95%CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6% (95%CI 5-7%). The risk of composite adverse outcome was similar using the first or subsequent UCR values. Conclusion An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7% when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.
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- Stampalija, T., et al.
(författare)
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Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction : prospective cohort study
- 2020
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:2, s. 173-181
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. Methods This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32+ 0 to 36+ 6weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. Results The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n= 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33weeks and 1.0 at 34-36weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. Conclusion In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. (C) 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
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- Ichioka, Yuki, et al.
(författare)
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Decontamination of biofilm-contaminated implant surfaces: An in vitro evaluation
- 2023
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Ingår i: Clinical Oral Implants Research. - 0905-7161. ; 34:10, s. 1058-1072
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of the present study was to evaluate the cleaning efficacy of two mechanical and two chemical protocols in the decontamination of implant surfaces.Methods: In total, 123 commercially available implants were mounted in plastic models mimicking peri-implant circumferential intra-bony defects. A multispecies biofilm was grown on implant surfaces. Mechanical (air-polishing (AP), rotating titanium brush (TiB)) and chemical decontamination (alkaline electrolyzed water, N-acetyl-L-cysteine) protocols were used. Cleaning efficacy in terms of residual biofilm area, chemical surface properties, and bacterial counts were analyzed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and quantitative polymerase chain reaction.Results: Surface decontamination protocols including use of an AP device or a rotating TiB were superior in terms of biofilm removal and in reducing atomic% of Carbon on implant surfaces when compared to methods restricted to wiping with gauze. The use of chemical agents as adjuncts to the mechanical cleaning protocols provided no relevant overall benefit over saline. No treatment modality, however, resulted in complete biofilm removal.Conclusion: Air-polishing and rotating TiB were more effective implant surface decontamination protocols than wiping with gauzes. Use of chemical agents did not improve cleaning efficacy.
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- Suvan, J, et al.
(författare)
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Subgingival Instrumentation for Treatment of Periodontitis. A Systematic Review.
- 2020
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 47:Suppl 22, s. 155-75
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Forskningsöversikt (refereegranskat)abstract
- To evaluate the efficacy of subgingival instrumentation (PICOS-1), sonic/ultrasonic/hand instruments (PICOS-2) and different subgingival instrumentation delivery protocols (PICOS-3) to treat periodontitis.Systematic electronic search (CENTRAL/MEDLINE/EMBASE/SCOPUS/LILACS) to March 2019 was conducted to identify randomized controlled trials (RCT) reporting on subgingival instrumentation. Duplicate screening and data extraction were performed to formulate evidence tables and meta-analysis as appropriate.As only one RCT addressed the efficacy of subgingival instrumentation compared to supragingival cleaning alone (PICOS-1), baseline and final measures from 11 studies were considered. The weighted pocket depth (PD) reduction was 1.7 mm (95%CI: 1.3-2.1) at 6/8 months and the proportion of pocket closure was estimated at 74% (95%CI: 64-85). Six RCTs compared hand and sonic/ultrasonic instruments for subgingival instrumentation (PICOS-2). No significant differences were observed between groups by follow-up time point or category of initial PD. Thirteen RCTs evaluated quadrant-wise vs full-mouth approaches (PICOS-3). No significant differences were observed between groups irrespective of time-points or initial PD. Five studies reported patient-reported outcomes, reporting no differences between groups.Nonsurgical periodontal therapy by mechanical subgingival instrumentation is an efficacious means to achieve infection control in periodontitis patients irrespective of the type of instrument or mode of delivery. Prospero ID:CRD42019124887.
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- Tomasi, Cristiano, 1964, et al.
(författare)
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Efficacy of rehabilitation of stage IV periodontitis patients with full-arch fixed prostheses: Tooth-supported versus Implant-supported-A systematic review
- 2022
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 49:Suppl 24, s. 248-271
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Forskningsöversikt (refereegranskat)abstract
- Objectives To evaluate the efficacy of implant-supported in comparison to tooth-supported full-arch prostheses in patients with stage IV periodontitis. Materials and Methods Systematic electronic search (CENTRAL/MEDLINE/SCOPUS) up to March 2020 was conducted to identify randomized controlled trials and cohort-like studies comparing/evaluating fixed full-arch rehabilitation on teeth or implants in patients with stage IV periodontitis. The primary outcome measure was loss of teeth/implants and restorations. Data extraction was performed to create evidence tables, and meta-analyses were carried out as appropriate. Results A total of 26 studies (31 publications) were identified but none addressed the scientific question in a controlled and randomized design. The risk of bias throughout the included studies was judged to be high, and meta-analyses demonstrated a high degree of heterogeneity. Mean-weighted observation periods in studies on tooth-supported restorations were significantly longer than in studies on implant-supported restorations. The predicted loss of teeth and tooth-supported full-arch restorations over 10 years was 1% and 5%, respectively. The 15-year estimates were 10% and 13%. Corresponding predictions for implants and implant-supported restorations for 10 years amounted to 4% and 6%, respectively. Technical complications were the most commonly reported and affected 8% of tooth-supported restorations (during 7.2 years) and 42% of implant-supported structures (during 2.6 years). Peri-implantitis- or peri-implantitis-like symptoms were observed at an estimated 9% of implants (after 3.1 years). Conclusions Based on observational studies on full-arch rehabilitation of stage IV periodontitis patients, 10-year estimates of tooth loss were lower than the corresponding estimates for implants. Estimated loss of tooth- and implant-supported restorations at 10 years was similar. Technical complications were more prevalent at implant-supported when compared to tooth-supported restorations.
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| 16. |
- Tonetti, M. S., et al.
(författare)
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Relevant domains, core outcome sets and measurements for implant dentistry clinical trials: The Implant Dentistry Core Outcome Set and Measurement (ID-COSM) international consensus report
- 2023
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Ingår i: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 50:suppl. 25, s. 5-21
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). Materials and Methods: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. Results: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying prespecified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). Conclusions: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.
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