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  • Ahlin, Sofie, 1985, et al. (författare)
  • Fracture risk after three bariatric surgery procedures in Swedish obese subjects: up to 26 years follow-up of a controlled intervention study.
  • 2020
  • Ingår i: Journal of internal medicine. - : Wiley-Blackwell. - 1365-2796. ; 287:5, s. 546-557
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have reported an increased fracture risk after bariatric surgery.To investigate the association between different bariatric surgery procedures and fracture risk.Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups.During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02-3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41-2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66-2.79; P < 0.001).The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
  • Watt, F. E., et al. (författare)
  • Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
  • 2019
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584. ; 27:1, s. 23-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
  • Semb, Gunvor, et al. (författare)
  • A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
  • 2017
  • Ingår i: Journal of plastic surgery and hand surgery. - : Taylor & Francis. - 2000-6764 .- 2000-656X. ; 51:1, s. 2-13
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.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.Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.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.ISRCTN29932826.
  • Styrkarsdottir, Unnur, et al. (författare)
  • Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
  • 2017
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036. ; 49:5, s. 801-805
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
  • Hammarström, I. L., et al. (författare)
  • Scandcleft Project Trial 2—Comparison of Speech Outcome in 1- and 2-Stage Palatal Closure in 5-Year-Olds With UCLP
  • 2020
  • Ingår i: Cleft Palate-Craniofacial Journal. - : Sage Publications. - 1055-6656 .- 1545-1569. ; 57:4, s. 458-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate in-depth speech results in the Scandcleft Trial 2 with comparisons between surgical protocols and centers and with benchmarks from peers without cleft palate. Design: A prospective randomized clinical trial. Setting: Two Swedish and one Finnish Cleft Palate center. Participants: One hundred twelve participants were 5-years-old born with unilateral cleft lip and palate randomized to either lip repair and soft palate closure at 4 months and hard palate closure at 12 months or lip repair at 3 to 4 months (Arm A), or a closure of both the soft and hard palate at 12 months (Arm C). Main Outcome Measures: A composite measure dichotomized into velopharyngeal competency (VPC) or velopharyngeal incompetency (VPI), overall assessment of velopharyngeal function (VPC-Rate), percentage of consonants correct (PCC score), and consonant errors. In addition, number of speech therapy visits, average hearing thresholds, and secondary surgeries were documented to assess burden of treatment. Results: Across the trial, 53.5% demonstrated VPC and 46.5% VPI with no significant differences between arms or centers. In total, 27% reached age-appropriate PCC scores with no statistically significant difference between the arms. The Finnish center had significantly higher PCC scores, the Swedish centers had higher percentages of oral consonant errors. Number of speech therapy visits was significantly higher in the Finnish center. Conclusion: At age 5, poor speech outcomes with some differences between participating centers were seen but could not be attributed to surgical protocol. As one center had very few participants, the results from that center should be interpreted with caution. © 2019, American Cleft Palate-Craniofacial Association.
  • Michaëlsson, K, et al. (författare)
  • Association between statin use and consultation or surgery for osteoarthritis of the hip or knee : A pooled analysis of four cohort studies
  • 2017
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 25:11, s. 1804-1813
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Experimental findings and previous observational data have suggested lower risk of osteoarthritis (OA) with statin use but results are inconsistent. Large-scale studies with a clinically important outcome are needed. Thus, we aimed to determine whether statin use is associated with a reduced risk of developing clinically-defined hip or knee OA. Design: Pooled analysis based on time-to-event analysis of four population-based large cohorts, encompassing in total 132,607 persons aged 57-91 years resident in southern and central Sweden. We studied the association between statin use and time to consultation or surgery for OA of the hip or knee by time-dependent exposure analysis and Cox regression. Results: During 7.5 years of follow-up, we identified 7468 out- or inpatient treated cases of hip or knee OA. Compared with never use, current use of statins conferred no overall reduction in the risk of OA with an adjusted pooled hazard ratio (HR) of 1.04 (95% confidence intervals [95% CI] 0.99-1.10). We found no dose-response relation between duration of current statin use and the risk of OA, with similar HRs among patients with less than 1 year of use (HR 1.09; 95% CI 0.92-1.32) as in patients with use for 3 years or more (HR 1.05; 0.93-1.16). Results were comparable in those with low, medium and high dose of current statin use, without indications of heterogeneity of study results. Conclusion: Statin use is not associated with reduced risk of consultation or surgery for OA of the hip or knee.
  • Semb, G, et al. (författare)
  • Erratum
  • 2017
  • Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 141:1, s. E1-E4
  • Tidskriftsartikel (refereegranskat)
  • Chockalingam, P. S., et al. (författare)
  • Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor
  • 2011
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584. ; 19:3, s. 315-323
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate aggrecanase activity after traumatic knee injury in a rat model by measuring the level of aggrecanase-generated Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments in synovial fluid, and compare with ARG-aggrecan release into joint fluid following human knee injury. To evaluate the effect of small molecule inhibitors on induced aggrecanase activity in the rat model. Method: An enzyme-linked immunosorbent assay (ELISA) was developed to measure ARG-aggrecan levels in animal and human joint fluids. A rat model of meniscal tear (MT)-induced joint instability was used to assess ARG-aggrecan release into joint fluid and the effects of aggrecanase inhibition. Synovial fluids were also obtained from patients with acute joint injury or osteoarthritis and assayed for ARG-aggrecan. Results: Joint fluids from human patients after knee injury showed significantly enhanced levels of ARG-aggrecan compared to uninjured reference subjects. Similarly, synovial fluid ARG-aggrecan levels increased following surgically-induced joint instability in the rat MT model, which was significantly attenuated by orally dosing the animals with AGG-523, an aggrecanase specific inhibitor. Conclusions: Aggrecanase-generated aggrecan fragments were rapidly released into human and rat joint fluids after injury to the knee and remained elevated over a prolonged period. Our findings in human and preclinical models strengthen the connection between aggrecanase activity in joints and knee injury and disease. The ability of a small molecule aggrecanase inhibitor to reduce the release of aggrecanase-generated aggrecan fragments into rat joints suggests that pharmacologic inhibition of aggrecanase activity in humans may be an effective treatment for slowing cartilage degradation following joint injury. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  • Chockalingam, P. S., et al. (författare)
  • Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation
  • 2013
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584. ; 21:2, s. 339-345
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: We have previously shown the capacity of tenascin-C (TN-C) to induce inflammatory mediators and matrix degradation in vitro in human articular cartilage. The objective of the present study was to follow TN-C release into knee synovial fluid after acute joint injury or in joint disease, and to correlate TN-C levels with markers of cartilage matrix degradation and inflammation. Method: Human knee synovial fluid samples (n = 164) were from a cross-sectional convenience cohort. Diagnostic groups were knee healthy reference, knee anterior cruciate ligament rupture, with or without concomitant meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints of dogs that underwent knee instability surgery. Results: Statistically significantly higher levels of TN-C compared to reference subjects were observed in the joint fluid of all human disease groups and in the dogs that underwent knee instability surgery. Statistically significant correlations were observed between the TN-C levels in the synovial fluid of the human patients and the levels of aggrecanase-dependent Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and 3. Conclusions: We find highly elevated levels of TN-C in human knee joints after injury, AIA or OA that correlated with markers of cartilage degradation and inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint damage and a stimulant of further joint degradation. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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