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- 2019
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Tidskriftsartikel (refereegranskat)
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- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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- Ardern, Clare L, et al.
(författare)
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Implementing the 27 PRISMA 2020 Statement items for systematic reviews in the sport and exercise medicine, musculoskeletal rehabilitation and sports science fields : The PERSiST (implementing Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science) guidance
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:4, s. 175-195
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Tidskriftsartikel (refereegranskat)abstract
- Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.
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- Dittrich, Sabine, et al.
(författare)
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Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings : An Expert Consensus
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40 degrees C, <= 90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40 degrees C, <= 90% non-condensing humidity; and iv) minimal sample collection needs (50-100 mu L, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.
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- Karjalainen, Teemu V., et al.
(författare)
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Subacromial decompression surgery for rotator cuff disease
- 2019
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Ingår i: Cochrane Database of Systematic Reviews. - : WILEY. - 1469-493X. ; :1
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Forskningsöversikt (refereegranskat)abstract
- Background Surgery for rotator cuff disease is usually used after non-operative interventions have failed, although our Cochrane Review, first published in 2007, found that there was uncertain clinical benefit following subacromial decompression surgery. Objectives To synthesise the available evidence of the benefits and harms of subacromial decompression surgery compared with placebo, no intervention or non-surgical interventions in people with rotator cuff disease (excluding full thickness rotator cuff tears). Search methods We searched CENTRAL, MEDLINE, Embase, Clinicaltrials. gov and WHO ICRTP registry from 2006 until 22 October 2018, unrestricted by language. Selection criteria We included randomised and quasi-randomised controlled trials (RCTs) of adults with rotator cuff disease (excluding full-thickness tears), that compared subacromial decompression surgery with placebo, no treatment, or any other non-surgical interventions. As it is least prone to bias, subacromial decompression compared with placebo was the primary comparison. Other comparisons were subacromial decompression versus exercises or non-operative treatment. Major outcomes were mean pain scores, shoulder function, quality of life, participant global assessment of success, adverse events and serious adverse events. The primary endpoint for this review was one year. For serious adverse events, we also included data from prospective cohort studies designed to record harms that evaluated subacromial decompression surgery or shoulder arthroscopy. Data collection and analysis We used standard methodologic procedures expected by Cochrane. Main results We included eight trials, with a total of 1062 randomised participants with rotator cuff disease, all with subacromial impingement. Two trials (506 participants) compared arthroscopic subacromial decompression with arthroscopy only (placebo surgery), with all groups receiving postoperative exercises. These trials included a third treatment group: no treatment (active monitoring) in one and exercises in the other. Six trials (556 participants) compared arthroscopic subacromial decompression followed by exercises with exercises alone. Two of these trials included a third arm: sham laser in one and open subacromial decompression in the other. Trial size varied from 42 to 313 participants. Participant mean age ranged between 42 and 65 years. Only two trials reported mean symptom duration (18 to 22 months in one trial and 30 to 31 months in the other), two did not report duration and four reported it categorically. Both placebo-controlled trials were at low risk of bias for the comparison of surgery versus placebo surgery. The other trials were at high risk of bias for several criteria, most notably at risk of performance or detection bias due to lack of participant and personnel blinding. We have restricted the reporting of results of benefits in the Abstract to the placebo-controlled trials. Compared with placebo, high-certainty evidence indicates that subacromial decompression provides no improvement in pain, shoulder function, or health-related quality of life up to one year, and probably no improvement in global success (moderate-certainty evidence, downgraded due to imprecision). At one year, mean pain (on a scale zero to 10, higher scores indicate more pain), was 2.9 points after placebo surgery and 0.26 better (0.84 better to 0.33 worse), after subacromial decompression (284 participants), an absolute difference of 3%(8% better to 3% worse), and relative difference of 4% (12% better to 5% worse). At one year, mean function (on a scale 0 to 100, higher score indicating better outcome), was 69 points after placebo surgery and 2.8 better (1.4 worse to 6.9 better), after surgery (274 participants), an absolute difference of 3% (7% better to 1% worse), and relative difference of 9% (22% better to 4% worse). Global success rate was 97/148 (or 655 per 1000), after placebo and 101/142 (or 708 per 1000) after surgery corresponding to RR 1.08 (95% CI 0.93 to 1.27). Healthrelated quality of life was 0.73 units (European Quality of Life EQ-5D, -0.59 to 1, higher score indicating better quality of life), after placebo and 0.03 units worse (0.011 units worse to 0.06 units better), after subacromial decompression (285 participants), an absolute difference of 1.3% (5% worse to 2.5% better), and relative difference of 4% (15% worse to 7% better). Adverse events including frozen shoulder or transientminor complications of surgery were reported in approximately 3% of participants across treatment groups in two randomised controlled trials, but due to low event rates we are uncertain if the risks differ between groups: 5/165 (37 per 1000) reported adverse events with subacromial decompression and 9/241 (34 per 1000) with placebo or nonoperative treatment, RR 0.91 (95% CI 0.31 to 2.65) (moderate-certainty evidence, downgraded due to imprecision). The trials did not report serious adverse events. Based upon moderate-certainty evidence from two observational trials from the same prospective surgery registry, which also included other shoulder arthroscopic procedures (downgraded for indirectness), the incidence proportion of serious adverse events within 30 days following surgery was 0.5% (0.4% to 0.7%; data collected 2006 to 2011), or 0.6% (0.5 % to 0.7%; data collected 2011 to 2013). Serious adverse events such as deep infection, pulmonary embolism, nerve injury, and death have been observed in participants following shoulder surgery. Authors conclusions The data in this review do not support the use of subacromial decompression in the treatment of rotator cuff disease manifest as painful shoulder impingement. High-certainty evidence shows that subacromial decompression does not provide clinically important benefits over placebo in pain, function or health-related quality of life. Including results from open-label trials (with high risk of bias) did not change the estimates considerably. Due to imprecision, we downgraded the certainty of the evidence to moderate for global assessment of treatment success; there was probably no clinically important benefit in this outcome either compared with placebo, exercises or non-operative treatment. Adverse event rates were low, 3% or less across treatment groups in the trials, which is consistent with adverse event rates reported in the two observational studies. Although precise estimates are unknown, the risk of serious adverse events is likely less than 1%.
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| 9. |
- Wang, Page I., et al.
(författare)
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Perfusion-weighted MR Imaging in Cerebral Lupus Erythematosus
- 2012
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Ingår i: Academic Radiology. - : Elsevier BV. - 1878-4046 .- 1076-6332. ; 19:8, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Rationale and Objective: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a diagnostically challenging, severe, and life-threatening condition, which is currently lacking a "gold standard." Our aim with this study is to look for magnetic resonance (MR) perfusion differences in NPSLE, SLE, and healthy control (HC) patients and correlate our findings with clinical parameters. Materials and Methods: Twenty-four NPSLE patients, 21 SLE patients, and 21 HC underwent dynamic susceptibility contrast enhanced MR perfusion using a 3-T scanner. Nine prospectively selected intracranial regions of interest were placed in white and gray matter and the cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MU) values were calculated. Subjects underwent clinical evaluation with SLEDAI and serum antibodies. Results: The SLE patients had higher CBF and CBV compared to the HC overall (P =.01) and in specific areas (P =.03-.048). SLE patients with signs of active disease (elevated SLEDAI and anti-double-stranded DNA) had significantly elevated CBV, CBF, and MU in the posterior cingulate gyrus (P =.01-.02). No significant difference was seen in the magnetic resonance perfusion measurements of NPSLE patients compared to SLE and HC, although the NPSLE patients also showed higher CBV variability compared to the SLE (P =.0004) and HC cohort (P <.0001). Conclusion: SLE patients have increased CBV and CBF compared to healthy controls. The SLE patients with clinical markers for active disease have elevated CBV, CBF, and MU in the posterior cingulate gyrus. NPSLE patients show increased variability in perfusion measurements, which may explain why susceptibility contrast enhanced MRI has not yet provided a specific target for NPSLE.
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