| 1. |
|
|
| 2. |
- 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 BV. - 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.
|
|
| 3. |
|
|
| 4. |
- Struglics, A., et al.
(författare)
-
Molecular and imaging biomarkers of local inflammation at 2 years after anterior cruciate ligament injury do not associate with patient reported outcomes at 5 years
- 2020
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:3, s. 356-362
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. Methods: For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. Results: None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. Conclusion: Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.
|
|
| 5. |
- Biel, D., et al.
(författare)
-
sTREM2 is associated with amyloid-related p-tau increases and glucose hypermetabolism in Alzheimer's disease
- 2023
-
Ingår i: Embo Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 15:2
-
Tidskriftsartikel (refereegranskat)abstract
- Microglial activation occurs early in Alzheimer's disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Here, we used CSF sTREM2 to investigate disease stage-dependent drivers of microglial activation and to determine downstream consequences on AD progression. We included 402 patients with measures of earliest beta-amyloid (CSF A beta(1-42)) and late-stage fibrillary A beta pathology (amyloid-PET centiloid), as well as sTREM2, p-tau(181), and FDG-PET. To determine disease stage, we stratified participants into early A beta-accumulators (A beta CSF+/PET-; n = 70) or late A beta-accumulators (A beta CSF+/PET+; n = 201) plus 131 controls. In early A beta-accumulators, higher centiloid was associated with cross-sectional/longitudinal sTREM2 and p-tau(181) increases. Further, higher sTREM2 mediated the association between centiloid and cross-sectional/longitudinal p-tau(181) increases and higher sTREM2 was associated with FDG-PET hypermetabolism. In late A beta-accumulators, we found no association between centiloid and sTREM2 but a cross-sectional association between higher sTREM2, higher p-tau(181) and glucose hypometabolism. Our findings suggest that a TREM2-related microglial response follows earliest A beta fibrillization, manifests in inflammatory glucose hypermetabolism and may facilitate subsequent p-tau(181) increases in earliest AD.
|
|
| 6. |
- Brown, Jamie S., et al.
(författare)
-
Clinical, patient-reported, radiographic and magnetic resonance imaging findings 11 years after acute posterior cruciate ligament injury treated non-surgically
- 2023
-
Ingår i: BMC Musculoskeletal Disorders. - 1471-2474. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term consequences of posterior cruciate ligament (PCL) injury such as persistent posterior tibial translation and risk of osteoarthritis development are unclear. Additionally, little data is available describing the natural history of structural morphology of the ruptured PCL. The purpose of the study was to determine the long-term outcome after non-operatively treated PCL injury. Methods: Over 6-years, all acute knee injuries were documented by subacute MRI (median 8 days [5–15, 25th − 75th percentile] from injury to MRI). Twenty-six patients with acute PCL injury were identified of whom 18 (69%) participated in the long-term follow-up after 11 years. Follow-up included radiographic posterior tibial translation (RPTT) determined using the Puddu axial radiograph. weight-bearing knee radiographs, MRI and KOOS (Knee injury and Osteoarthritis Outcome Score). Results: On subacute MRI, 11 knees displayed total and 7 partial ruptures. At 11 (SD 1.9) years, the median RPTT was 3.7 mm (1.5–6.3, 25th − 75th percentile). Seven knees displayed radiographic osteoarthritis approximating Kellgren-Lawrence grade ≥ 2. All follow-up MRIs displayed continuity of the PCL. Patients with more severe RPTT (> 3.7 mm), had worse scores in the KOOS subscales for symptoms (mean difference 14.5, 95% CI 7–22), sport/recreation (30, 95% CI 0–65) and quality of life (25, 95% CI 13–57) than those with less severe RPTT (≤ 3.7 mm). This was also the case for the KOOS4 (22, 95% CI 9–34). Conclusion: Acute PCL injuries treated non-surgically display a high degree of PCL continuity on MR images 11 years after injury. However, there is a large variation of posterior tibial translation with higher values being associated with poorer patient-reported outcomes.
|
|
| 7. |
|
|
| 8. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 9. |
|
|
| 10. |
- Richardson, Henry S., et al.
(författare)
-
Social Progress : A compass
- 2018
-
Ingår i: Rethinking Society for the 21st Century: Report of the International Panel on Social Progress. - : Cambridge University Press. - 9781108399623 ; , s. 41-80
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter sets out the main normative dimensions that should be used in assessing whether societies have made social progress and whether a given set of proposals is likely to bring progress. Some of these dimensions are values, bearing in the first instance on the evaluation of states of affairs; others are action-guiding principles. Values can inspire and in that sense also guide actions. Principles aim to offer more specific guidance on how to rank, distribute, and realize values. Recognizing a multiplicity of values and principles is important not only to being respectful of the variety of reasonable views about what matters but also because it is difficult to reduce the list of dimensions that ultimately matter to a shorter one in a way that reflects all aspects of the phenomena in question. Many of the chapters that follow will explicitly address only a subset of these values and principles: the ones most salient for their issues or areas; but in principle, all remain relevant.
|
|
| 11. |
|
|
| 12. |
- Santini, S., et al.
(författare)
-
System architectures and programming models
- 2008. - 2
-
Ingår i: Cooperating Embedded Systems and Wireless Sensor Networks. - : ISTE Publishing Company : John Wiley. - 1905209983 ; , s. 347-404
-
Bokkapitel (refereegranskat)
|
|
| 13. |
|
|
| 14. |
- Snoeker, B. A.M., et al.
(författare)
-
Is meniscal status in the anterior cruciate ligament injured knee associated with change in bone surface area? An exploratory analysis of the KANON trial
- 2021
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:6, s. 841-848
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study bone shape changes as a potential early feature of post-traumatic structural knee OA development, we estimated the association between meniscal status in the anterior cruciate ligament (ACL) injured knee and longitudinal condyle changes in bone surface area. Design: We used data from the KANON trial, including 121 young ACL-injured adults. We obtained baseline and 2-year follow-up knee MRIs. Our outcome was change in the bone surface areas (mean mm2, log-transformed) in 4 locations (femur, tibia, patella, and trochlea femur) in the medial and lateral compartment from baseline to 2 years. Meniscal pathology was defined as both present at baseline and newly developed (i.e., incident or progressed) using ACLOAS. We used multilevel linear regression adjusted for baseline bone area, age, sex, body mass index, treatment arm (i.e., early or optional delayed ACL reconstruction), and location. We analyzed medial and lateral compartment separately. We present results as percentage (%) bone area change difference with 95% confidence intervals (CI). Results: We analyzed 109 subjects (median 27 (18–36) years, 83% men) due to missing MRI information. The bone surface area increased on average by ∼2% over 2 years. The differences between knees with and without baseline meniscal pathology were 1.1% (95%CI 0.0–2.3%) and 1.4% (95%CI 0.6–2.2%) in the medial and lateral compartment, respectively, and 1.2% (95%CI 0.3–2.0%) and 1.3% (95%CI 0.6–2.0%) for medial and lateral newly developed pathology, respectively. Conclusion: Our finding of ∼1% increase bone area in compartment with meniscal pathology suggests a potentially important association between meniscal integrity and early bone surface area changes after ACL injury. Trial registration number ISRCTN 84752559.
|
|
| 15. |
|
|
| 16. |
- Whittaker, Jackie L., et al.
(författare)
-
Toward designing human intervention studies to prevent osteoarthritis after knee injury : A report from an interdisciplinary OARSI 2023 workshop
- 2024
-
Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.
|
|
