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| 2. |
- Bohm, Eric R., et al.
(författare)
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Collection and Reporting of Patient-reported Outcome Measures in Arthroplasty Registries: Multinational Survey and Recommendations
- 2021
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Ingår i: Clinical Orthopaedics and Related Research. - 0009-921X. ; 479:10, s. 2151-2166
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patient-reported outcome measures (PROMs) are validated questionnaires that are completed by patients. Arthroplasty registries vary in PROM collection and use. Current information about registry collection and use of PROMs is important to help improve methods of PROM data analysis, reporting, comparison, and use toward improving clinical practice. QUESTIONS/PURPOSES: To characterize PROM collection and use by registries, we asked: (1) What is the current practice of PROM collection by arthroplasty registries that are current or former members of the International Society of Arthroplasty Registries, and are there sufficient similarities in PROM collection between registries to enable useful international comparisons that could inform the improvement of arthroplasty care? (2) How do registries differ in PROM administration and demographic, clinical, and comorbidity index variables collected for case-mix adjustment in data analysis and reporting? (3) What quality assurance methods are used for PROMs, and how are PROM results reported and used by registries? (4) What recommendations to arthroplasty registries may improve PROM reporting and facilitate international comparisons? METHODS: An electronic survey was developed with questions about registry structure and collection, analysis, reporting, and use of PROM data and distributed to directors or senior administrators of 39 arthroplasty registries that were current or former members of the International Society of Arthroplasty Registries. In all, 64% (25 of 39) of registries responded and completed the survey. Missing responses from incomplete surveys were captured by contacting the registries, and up to three reminder emails were sent to nonresponding registries. Recommendations about PROM collection were drafted, revised, and approved by the International Society of Arthroplasty Registries PROMs Working Group members. RESULTS: Of the 25 registries that completed the survey, 15 collected generic PROMs, most frequently the EuroQol-5 Dimension survey; 16 collected joint-specific PROMs, most frequently the Knee Injury and Osteoarthritis Outcome Score and Hip Disability and Osteoarthritis Outcome Score; and 11 registries collected a satisfaction item. Most registries administered PROM questionnaires within 3 months before and 1 year after surgery. All 16 registries that collected PROM data collected patient age, sex or gender, BMI, indication for the primary arthroplasty, reason for revision arthroplasty, and a comorbidity index, most often the American Society of Anesthesiologists classification. All 16 registries performed regular auditing and reporting of data quality, and most registries reported PROM results to hospitals and linked PROM data to other data sets such as hospital, medication, billing, and emergency care databases. Recommendations for transparent reporting of PROMs were grouped into four categories: demographic and clinical, survey administration, data analysis, and results. CONCLUSION: Although registries differed in PROM collection and use, there were sufficient similarities that may enable useful data comparisons. The International Society of Arthroplasty Registries PROMs Working Group recommendations identify issues that may be important to most registries such as the need to make decisions about survey times and collection methods, as well as how to select generic and joint-specific surveys, handle missing data and attrition, report data, and ensure representativeness of the sample. CLINICAL RELEVANCE: By collecting PROMs, registries can provide patient-centered data to surgeons, hospitals, and national entities to improve arthroplasty care.
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| 3. |
- Essery, Rosie, et al.
(författare)
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The Development of Balance Retraining : An Online Intervention for Dizziness in Adults Aged 50 Years and Older
- 2015
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Ingår i: American Journal of Audiology. - : AMER SPEECH-LANGUAGE-HEARING ASSOC. - 1059-0889 .- 1558-9137. ; 24:3, s. 276-279
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This article outlines the rationale and development process for an online intervention based on vestibular rehabilitation therapy (VRT). The intervention aims to assist adults aged 50 years and older to self-manage and reduce dizziness symptoms. Method: The intervention was developed according to the person-based approach to digital intervention design focused on accommodating perspectives of target users. A prototype version of the intervention was provided to 18 adults (11 women, 7 men) aged 50 years and older with dizziness. These adults were invited to use the intervention over a 6-week period and, during this time, took part in a think-aloud session. This session sought to understand users' perceptions of how acceptable, engaging, and easy to use they found the online intervention. Results: Users were extremely positive regarding how easy to navigate, visually appealing, and informative they found the intervention. Think-aloud sessions provided valuable data for informing small amendments to further enhance acceptability of the intervention for target users. Conclusions: Informed by these development-phase data, a finalized version of the intervention is now being investigated in a primary care–based randomized controlled trial. Results should provide an understanding of whether VRT can be effectively—especially, cost-effectively—delivered via an online intervention to adults aged 50 years and older.
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| 4. |
- Fenner, Merle Friederike, et al.
(författare)
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Effect of selective IK,ACh inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation
- 2020
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:16, s. 3778-3794
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction. Key Results: XAF-1407 potently and selectively inhibited Kir3.1/3.4 and Kir3.4/3.4, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia. Conclusion and Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.
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- Geraghty, Adam W. A., et al.
(författare)
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Internet-based vestibular rehabilitation for adults aged 50 years and over: a protocol for a randomised controlled trial
- 2014
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Ingår i: BMJ Open. - : BMJ Publishing Group: Open Access / BMJ Journals. - 2044-6055. ; 4:7, s. e005871-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Dizziness is highly prevalent in older adults and can lead to falls, fear of falling, loss of confidence, anxiety and depression. Vestibular rehabilitation (VR) exercises are effective in reducing dizziness due to vestibular dysfunction, but access to trained therapists is limited. Providing dizzy patients with booklets teaching them how to carry out VR exercises has been shown to be a cost-effective way of managing dizziness in primary care. Internet-based intervention delivery has many advantages over paper-based methods, including the provision of video instructions, automated tailoring and symptom-related feedback. This trial will examine whether an internet-based VR intervention is (1) effective in reducing dizziness and (2) a cost-effective primary care treatment option. Methods/analysis: This will be a single blind, randomised controlled trial carried out in UK primary care. A stand-alone internet-based VR intervention will be compared with routine care in 262 dizzy patients aged 50 years and over. Measures will be taken at baseline, 3 and 6 months. Our primary outcome measure will be the effectiveness of the intervention in reducing dizziness symptoms compared with routine care at 6 months. Cost-effectiveness will be examined along with the effect of the intervention on dizziness-related disability and symptoms of depression and anxiety. Psychological process variables including expectancy, self-efficacy and acceptance will be explored in relation to adherence and symptom reduction. Ethics/dissemination: This trial has undergone ethical scrutiny and been approved by an NHS Research Ethics Committee, Southampton A REC Reference: 13/SC/0119. The findings of this trial will be disseminated to the scientific community through presentations at national and international conferences, and by publishing in peer review journals. Findings will be disseminated to the public through targeted press releases. This trial will provide valuable information on the role of internet interventions in facilitating self-management in older adults.
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| 6. |
- Geraghty, Adam W. A., et al.
(författare)
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Internet-Based Vestibular Rehabilitation for Older Adults With Chronic Dizziness : A Randomized Controlled Trial in Primary Care
- 2017
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Ingår i: Annals of Family Medicine. - : Annals of Family Medicine. - 1544-1709 .- 1544-1717. ; 15:3, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Vestibular rehabilitation is an effective intervention for dizziness due to vestibular dysfunction, but is seldom provided. We aimed to determine the effectiveness of an Internet-based vestibular rehabilitation program for older adults experiencing dizziness in primary care.METHODS: We undertook a single-center, single-blind randomized controlled trial comparing an Internet-based vestibular rehabilitation intervention (Balance Retraining, freely available from https://balance.lifeguidehealth.org) with usual primary care in patients from 54 primary care practices in southern England. Patients aged 50 years and older with current dizziness exacerbated by head movements were enrolled. Those in the intervention group accessed an automated Internet-based program that taught vestibular rehabilitation exercises and suggested cognitive behavioral management strategies. Dizziness was measured by the Vertigo Symptom Scale–Short Form (VSS-SF) at baseline, 3 months, and 6 months. The primary outcome was VSS-SF score at 6 months.RESULTS: A total of 296 patients were randomized in the trial; 66% were female, and the median age was 67 years. The VSS-SF was completed by 250 patients (84%) at 3 months and 230 patients (78%) at 6 months. Compared with the usual care group, the Internet-based vestibular rehabilitation group had less dizziness on the VSS-SF at 3 months (difference, 2.75 points; 95% CI, 1.39–4.12; P <.001) and at 6 months (difference, 2.26 points; 95% CI, 0.39–4.12; P = .02, respectively). Dizziness-related disability was also lower in the Internet-based vestibular rehabilitation group at 3 months (difference, 6.15 points; 95% CI, 2.81–9.49; P <.001) and 6 months (difference, 5.58 points; 95% CI, 1.19–10.0; P = .01).CONCLUSIONS: Internet-based vestibular rehabilitation reduces dizziness and dizziness-related disability in older primary care patients without requiring clinical support. This intervention has potential for wide application in community settings.
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| 7. |
- Haniffa, Muzlifah, et al.
(författare)
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A roadmap for the Human Developmental Cell Atlas
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597:7875, s. 196-205
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Tidskriftsartikel (refereegranskat)abstract
- This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved. The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
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| 8. |
- Matuozzo, Daniela, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
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| 9. |
- Verheyen, Kris, et al.
(författare)
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201 Combining Biodiversity Resurveys across Regions to Advance Global Change Research
- 2017
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:1, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- More and more ecologists have started to resurvey communities sampled in earlier decades to determine long-term shifts in community composition and infer the likely drivers of the ecological changes observed. However, to assess the relative importance of and interactions among multiple drivers, joint analyses of resurvey data from many regions spanning large environmental gradients are needed. In this article, we illustrate how combining resurvey data from multiple regions can increase the likelihood of driver orthogonality within the design and show that repeatedly surveying across multiple regions provides higher representativeness and comprehensiveness, allowing us to answer more completely a broader range of questions. We provide general guidelines to aid the implementation of multiregion resurvey databases. In so doing, we aim to encourage resurvey database development across other community types and biomes to advance global environmental change research.
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