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- Pulit, S. L., et al.
(författare)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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- Marini, S., et al.
(författare)
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Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
- 2019
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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- Hinman, R. S., et al.
(författare)
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Development of a core capability framework for qualified health professionals to optimise care for people with osteoarthritis : an OARSI initiative
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:2, s. 154-166
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Develop a generic trans-disciplinary, skills-based capability framework for health professionals providing care for people with OA. Design: e-Delphi survey. An international inter-professional Delphi Panel (researchers; clinicians; consumer representatives) considered a draft framework (adapted from elsewhere) of 131 specific capabilities mapped to 14 broader capability areas across four domains (A: person-centred approaches; B: assessment, investigation and diagnosis; C: management, interventions and prevention; D: service and professional development). Over three rounds, the Panel rated their agreement (Likert or numerical rating scales) on whether each specific capability in Domains B and C was essential (core) for all health professionals when providing care for all people with OA. Those achieving consensus (≥80% of Panel) rating of ≥ seven out of ten (Round 3) were retained. Generic domains (A and D) were included in the final framework and amended based on Panel comments. Results: 173 people from 31 countries, spanning 18 disciplines and including 26 consumer representatives, participated. The final framework comprised 70 specific capabilities across 13 broad areas i) communication; ii) person-centred care; iii) history-taking; iv) physical assessment; v) investigations and diagnosis; vi) interventions and care planning; vii) prevention and lifestyle interventions; viii) self-management and behaviour change; ix) rehabilitative interventions; x) pharmacotherapy; xi) surgical interventions; xii) referrals and collaborative working; and xiii) evidence-based practice and service development). Conclusion: Experts agree that health professionals require an array of skills in person-centred approaches; assessment, investigation and diagnosis; management, interventions and prevention; and service and professional development to provide optimal care for people with OA.
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- Zhang, W., et al.
(författare)
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EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:1, s. 8-17
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Forskningsöversikt (refereegranskat)abstract
- Objectives: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. Results: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR,10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. Conclusion: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
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- Zhang, W., et al.
(författare)
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EULAR evidence based recommendations for the management of hand osteoarthritis: report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT)
- 2007
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 66:3, s. 377-388
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop evidence based recommendations for the management of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. Results: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. Conclusion: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.
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- Allen, K. D., et al.
(författare)
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Osteoarthritis: Models for appropriate care across the disease continuum
- 2016
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Ingår i: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 30:3, s. 503-535
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is a leading cause of pain and disability worldwide. Despite the existence of evidence-based treatments and guidelines, substantial gaps remain in the quality of OA management. There is underutilization of behavioral and rehabilitative strategies to prevent and treat OA as well as a lack of processes to tailor treatment selection according to patient characteristics and preferences. There are emerging efforts in multiple countries to implement models of OA care, particularly focused on improving nonsurgical management. Although these programs vary in content and setting, key lessons learned include the importance of support from all stakeholders, consistent program delivery and tools, a coherent team to run the program, and a defined plan for outcome assessment. Efforts are still needed to develop, deliver, and evaluate models of care across the spectrum of OA, from prevention through end-stage disease, in order to improve care for this highly prevalent global condition. © 2016
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| 16. |
- Eyles, J.P., et al.
(författare)
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Clinical Outcomes Of Osteoarthritis Management Programs: A Project Of The Oa Trial Bank And Oarsi Joint Effort Initiative Using Individual Participant Data
- 2023
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 31, s. S385-S386
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: People living with osteoarthritis (OA) often do not receive best evidence care. Coordinated OA management programs (OAMPs) have been implemented to address this global evidence-practice gap. An OAMP is defined as a package of care with the following: i) a personalized management plan; ii) with reassessment and progression; iii) using a minimum of 2 core treatments (education, exercise, weight control), and; iv) optional adjunctive therapies. Existing OAMP models differ in treatment mode, intensity, duration, the health professionals delivering care, and the healthcare systems and settings they operate within. Randomized trials (RCTs) and cohort studies assess the outcomes of different OAMPs, however, these models are unlikely to ever be compared in RCTs due to the huge expense and complicated logistics required. Prognosis research provides another method of comparing outcomes of different OAMP models. This study aimed to estimate the pain and self-reported function outcomes (at 12-, 26- and 52-weeks) of people with hip and/or knee OA who participated in international OAMPs. It also aimed to describe the characteristics of OAMP participants.Methods: This study was undertaken by members of the OARSI Joint Effort Initiative (JEI), in collaboration with the OA Trial Bank (Erasmus MC, Netherlands). RCTs and clinical cohorts assessing OAMPs were identified through the JEI membership and literature searches. Eligible studies included data from an ongoing OAMP, in any real-world setting, with participants who were diagnosed with hip or knee OA, and longitudinal measures of patient-reported pain and function. The investigators of eligible studies were invited to complete data delivery agreements with the OA Trial Bank, share individual participant data (IPD), contribute to study design and authorship. Investigators ensured they had local ethics review board approval to contribute IPD to the OA Trial bank. Each dataset was converted to a common format to enable merging into one dataset. The IPD were evaluated to convert pain and function variables to standardized scales as appropriate. Pain scores were converted to a 0-100 point scale (100 worst). Function scores were converted to a 0-100 point scale (100 best). A generalized estimating equations (GEE) model analysis was performed to assess the change in pain and function from baseline across weeks 12, 26, and 52. The model specification was based on an unstructured correlation structure and robust standard errors. Pain and function estimates were adjusted by age, sex and body mass index (BMI). Data analyses were carried out using Stata 15 (StataCorp 2015) and SPSS 17.Results: The investigators of 13 international OAMPs were invited to take part. IPD from 9 OAMPs were delivered: the OA Chronic Care Program, Ramsay Health OA Management Program, Joint Health Program, University of Wisconsin Health Knee and Hip Comprehensive Non-Surgical OA Management Clinic, Improved Management of Patients With Hip and Knee OA in Primary Health Care, Joint Academy, Amsterdam OA cohort, Management of OA In Consultations, and Collaborative model of care between Orthopaedics and allied healthcare professionals in knee OA. The characteristics of the OAMPs are summarised in table 1. The OAMPs were conducted in-person except for the Joint Academy that was implemented as an online OAMP. Individual participant data from 9819 participants were analyzed. The cohort studies were missing large amounts of data, as expected in clinical practice. The characteristics of OAMP participants are summarised in Table 2. The majority of OAMP participants reported the knee as their index joint, their mean age ranged between 62- 67 years, 58-74% were female, 25-48% were working and mean BMI indicated they were overweight at baseline. Pain was most commonly assessed using a Numeric Rating Scale or validated questionnaires e.g. the Knee Injury and OA Outcome Scale (KOOS). Function was mostly assessed using validated questionnaires such as the KOOS. The pain and fuction measured in the original datasets are reported in Table 1. The changes in pain and function of the OAMP participants from baseline across weeks 12, 26, and 52 are summarised in Table 3. There were reductions in pain scores and improvements in function scores seen across all programs at the majority of timepoints.Conclusions: We established the first data bank of IPD from different international OAMPs. Analysis of the IPD demonstrated modest improvements in pain and function across the programs at all timepoints. The most rapid improvements were made by week-12, however, these gains were maintained at week-52. In future work this project will use IPD meta-analysis to identify prognostic factors of people with OA who participate in OAMPs.
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- Haugen, Ida K., et al.
(författare)
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Development of radiographic classification criteria for hand osteoarthritis : a methodological report (Phase 2)
- 2022
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesIn Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA.MethodsMultidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested.ResultsThe experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good.ConclusionRadiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets.
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| 20. |
- Stepniak, Karolina, et al.
(författare)
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Mapping chromatin accessibility and active regulatory elements reveals pathological mechanisms in human gliomas
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas. Gliomas are tumors often associated with epigenetics-related gene deregulation. Here the authors reveal an atlas of active enhancers and promoters in benign and malignant gliomas by performing whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples.
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