1. |
- Veerman, Rosanne E., et al.
(författare)
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Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin
- 2021
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Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are increasingly tested as therapeutic vehicles and biomarkers, but still EV subtypes are not fully characterised. To isolate EVs with few co-isolated entities, a combination of methods is needed. However, this is time-consuming and requires large sample volumes, often not feasible in most clinical studies or in studies where small sample volumes are available. Therefore, we compared EVs rendered by five commonly used methods based on different principles from conditioned cell medium and 250 mu l or 3 ml plasma, that is, precipitation (ExoQuick ULTRA), membrane affinity (exoEasy Maxi Kit), size-exclusion chromatography (qEVoriginal), iodixanol gradient (OptiPrep), and phosphatidylserine affinity (MagCapture). EVs were characterised by electron microscopy, Nanoparticle Tracking Analysis, Bioanalyzer, flow cytometry, and LC-MS/MS. The different methods yielded samples of different morphology, particle size, and proteomic profile. For the conditioned medium, Izon 35 isolated the highest number of EV proteins followed by exoEasy, which also isolated fewer non-EV proteins. For the plasma samples, exoEasy isolated a high number of EV proteins and few non-EV proteins, while Izon 70 isolated the most EV proteins. We conclude that no method is perfect for all studies, rather, different methods are suited depending on sample type and interest in EV subtype, in addition to sample volume and budget.
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2. |
- Danielsson, Henrik, et al.
(författare)
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A Systematic Review of Longitudinal Trajectories of Mental Health Problems in Children with Neurodevelopmental Disabilities
- 2024
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Ingår i: Journal of Developmental and Physical Disabilities. - : Springer. - 1056-263X .- 1573-3580. ; 36, s. 203-242
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Forskningsöversikt (refereegranskat)abstract
- To review the longitudinal trajectories - and the factors influencing their development - of mental health problems in children with neurodevelopmental disabilities. Systematic review methods were employed. Searches of six databases used keywords and MeSH terms related to children with neurodevelopmental disabilities, mental health problems, and longitudinal research. After the removal of duplicates, reviewers independently screened records for inclusion, extracted data (outcomes and influencing factors), and evaluated the risk of bias. Findings were tabulated and synthesized using graphs and a narrative. Searches identified 94,662 unique records, from which 49 publications were included. The median publication year was 2015. Children with attention deficit hyperactivity disorder were the most commonly included population in retrieved studies. In almost 50% of studies, trajectories of mental health problems changed by < 10% between the first and last time point. Despite multiple studies reporting longitudinal trajectories of mental health problems, greater conceptual clarity and consideration of the measures included in research is needed, along with the inclusion of a more diverse range of populations of children with neurodevelopmental disabilities.
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3. |
- Drott, Jenny, et al.
(författare)
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Patient preferences and experiences of participation in surgical cancer care
- 2022
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Ingår i: Worldviews on Evidence-Based Nursing. - : John Wiley & Sons. - 1545-102X .- 1741-6787. ; 19:5, s. 405-414
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Tidskriftsartikel (refereegranskat)abstract
- Background Quality cancer care necessitates opportunities for patient participation, supposedly recognizing the individual's preferences and experiences for being involved in their health and healthcare issues. Previous research shows that surgical cancer patients wish to be more involved, requiring professionals to be sensitive of patients' needs. Aims To explore preference-based patient participation in surgical cancer care. Methods A cross-sectional study was conducted. The Patient Preferences for Patient Participation tool (4Ps) was used, which includes 12 attributes of preferences for and experiences of patient participation. Data were analyzed with descriptive and comparative statistical methods. Results The results are based on a total of 101 questionnaires. Having reciprocal communication and being listened to by healthcare staff were commonly deemed crucial for patient participation. While 60% of the patients suggested that taking part in planning was crucial for their participation, they had experienced this only to some extent. Learning to manage symptoms and phrasing personal goals were items most often representing insufficient conditions for preference-based patient participation. Linking Evidence to Action To support person-centered surgical care, further efforts to suffice preference-based participation are needed, including opportunities for patients to share their experiences and engage in the planning of healthcare activities.
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4. |
- Eldh, Ann Catrine, Professor, 1965-, et al.
(författare)
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Facilitating facilitators to facilitate : Some general comments on a strategy for knowledge implementation in health services
- 2023
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Ingår i: Frontiers in Health Services. - : Frontiers Media S.A.. - 2813-0146. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Numerous endeavours to ensure that day-to-day healthcare is both evidence-based and person-centred have generated extensive, although partial, comprehension of what guarantees quality improvement. To address quality issues, researchers and clinicians have developed several strategies as well as implementation theories, models, and frameworks. However, more progress is needed regarding how to facilitate guideline and policy implementation that guarantees effective changes take place in a timely and safe manner. This paper considers experiences of engaging and supporting local facilitators in knowledge implementation. Drawing on several interventions, considering both training and support, this general commentary discusses whom to engage and the length, content, quantity, and type of support along with expected outcomes of facilitators' activities. In addition, this paper suggests that patient facilitators could help produce evidence-based and person-centred care. We conclude that research about the roles and functions of facilitators needs to include more structured follow-ups and also improvement projects. This can increase the speed of learning with respect to what works, for whom, in what context, why (or why not), and with what outcomes when it comes to facilitator support and tasks.
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5. |
- Eldh, Ann Catrine, 1965-, et al.
(författare)
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Kunskapsbaserad omvårdnad och implementering
- 2023. - 2
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Ingår i: Kvalitetsutveckling inom omvårdnad. - Lund : Studentlitteratur AB. - 9789144162164 ; , s. 129-162
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Forskningsresultat fyller en viktig funktion för att utveckla och bibehålla säker, effektiv och personcentrerad vård och omsorg. Trots kontinuerlig forskning är ett känt faktum att det kan ta lång tid från att ny kunskap framställs tills att nödvändiga forskningsresultat nyttiggörs i hälso- och sjukvård och omsorg. Studier visar att det kan ta upp till 17 år innan forskningsresultat får genomslag och blir till rutin i vårdens vardag. Implementeringsforskning är ett tvärprofessionellt forskningsområde där flera forskande sjuksköterskor har gjort betydelsefulla bidrag. Varför tar det så lång tid att implementera en omvårdnadsåtgärd eller omvårdnadsmetod och hur går det till att implementera ny eller annan relevant kunskap kommer att belysas i detta kapitel. Andra frågor som tas upp här är om det går att underlätta implementering och i så fall hur det kan möjliggöras.
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6. |
- Eldh, Ann Catrine, 1965-, et al.
(författare)
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Onset PrevenTIon of urinary retention in Orthopaedic Nursing and rehabilitation, OPTION-a study protocol for a randomised trial by a multi-professional facilitator team and their first-line managers' implementation strategy
- 2021
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Ingår i: Implementation Science. - : BioMed Central. - 1748-5908. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Onset PrevenTIon of urinary retention in Orthopaedic Nursing and rehabilitation, OPTION, project aims to progress knowledge translation vis-à-vis evidence-based bladder monitoring in orthopaedic care, to decrease the risk of urinary retention, and voiding complications. Urinary retention is common whilst in hospital for hip surgery. If not properly identified and managed, there is a high risk of complications, some lifelong and life threatening. Although evidence-based guidelines are available, the implementation is lagging.METHODS: Twenty orthopaedic sites are cluster randomised into intervention and control sites, respectively. The intervention sites assemble local facilitator teams among nursing and rehabilitation staff, including first-line managers. The teams receive a 12-month support programme, including face-to-face events and on-demand components to map and bridge barriers to guideline implementation, addressing leadership behaviours and de-implementation of unproductive routines. All sites have access to the guidelines via a public healthcare resource, but the control sites have no implementation support.Baseline data collection includes structured assessments of urinary retention procedures via patient records, comprising incidence and severity of voiding issues and complications, plus interviews with managers and staff, and surveys to all hip surgery patients with interviews across all sites. Further assessments of context include the Alberta Context Tool used with staff, the 4Ps tool for preference-based patient participation used with patients, and data on economic aspects of urinary bladder care.During the implementation intervention, all events are recorded, and the facilitators keep diaries. Post intervention, the equivalent data collections will be repeated twice, and further data will include experiences of the intervention and guideline implementation.Data will be analysed with statistical analyses, including comparisons before and after, and between intervention and control sites. The qualitative data are subjected to content analysis, and mixed methods are applied to inform both clinical outcomes and the process evaluation, corresponding to a hybrid design addressing effectiveness, experiences, and outcomes.DISCUSSION: The OPTION trial has a potential to account for barriers and enablers for guideline implementation in the orthopaedic context in general and hip surgery care in particular. Further, it may progress the understanding of implementation leadership by dyads of facilitators and first-line managers.TRIAL REGISTRATION: The study was registered as NCT04700969 with the U.S. National Institutes of Health Clinical Trials Registry on 8 January 2021, that is, prior to the baseline data collection.
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7. |
- Eldh, Maria, et al.
(författare)
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Proteomic Profiling of Tissue Exosomes Indicates Continuous Release of Malignant Exosomes in Urinary Bladder Cancer Patients, Even with Pathologically Undetectable Tumour
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:13
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Urinary bladder cancer (UBC) has a high recurrence rate, and biomarkers for different treatment strategies are highly needed. This study investigated the release of nanovesicles called exosomes from urinary bladder tissue from tumour-proximal sites as well as tumour-distant sites in transurethrally resected (TUR-B) patients with or without preoperative neoadjuvant chemotherapy prior to ensuing radical cystectomy-all without remaining visible tumour after TUR-B. We show that cancer-promoting exosomes were detected from both sites, suggesting that the previous tumour has altered the whole bladder tissue into a cancer-supporting milieu. The exosomes may originate from remaining pathologically undetectable cancer cells or transformed epithelial cells, and the study supports the notion of exosomes as mediators of metastatic spread and as potential biomarkers. It also supports early and radical removal of the bladder in urinary bladder cancer patients. Invasive urothelial bladder cancer (UBC) has high recurrence rates even after radical cystectomy (RC). Exosomes are membrane-bound nanovesicles, which have been shown to contribute to carcinogenesis and metastasis. We previously showed that urinary exosomes display a malignant profile in UBC patients despite the absence of detectable tumour. Here, we investigated exosomes from sampling sites close to or distant from the former tumour, aiming to understand the effect of the tumour on the local milieu. Ten patients scheduled for cystectomy after transurethral bladder resection (TUR-B), without remaining detectable tumour, were included. Exosomes were isolated from tissue explants of both the previous tumour site and distant bladder tissue. Proteins were quantified by mass spectrometry in seven patients. Exosomes from the previous tumour site were enriched in inflammatory but not cancer-related pathways compared to distant tissue. However, the 69 most abundant proteins in tissue-derived exosomes regardless of site, 20 of which were also found in urinary exosomes from our previous study, were enriched for cancer-related metabolic pathways and associated with poor prognosis in an external mRNA dataset. The enrichment of cancer-related pathways in the most abundant proteins, regardless of sampling site, confirms our hypothesis that despite the absence of detectable tumour, the entire bladder releases exosomes that contribute to metastasis and highlights the need for early RC.
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10. |
- Fjordkvist, Erika, 1985-, et al.
(författare)
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First-line managers' experience of guideline implementation during the COVID-19 pandemic
- 2024
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Ingår i: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648.
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Tidskriftsartikel (refereegranskat)abstract
- AIM(S): To explore first-line managers' experience of guideline implementation in orthopaedic care during the COVID-19 pandemic.DESIGN: A descriptive, qualitative study.METHODS: Semi-structured interviews with 30 first-line nursing and rehabilitation managers in orthopaedic healthcare at university, regional and local hospitals. The interviews were analysed by thematic analysis.RESULTS: First-line managers described the implementation of guidelines related to the pandemic as different from everyday knowledge translation, with a swifter uptake and time freed from routine meetings in order to support staff in adoption and adherence. The urgent need to address the crisis facilitated guideline implementation, even though there were specific pandemic-related barriers such as staffing and communication issues. An overarching theme, Hanging on to guidelines for dear life, is substantiated by three themes: Adapting to facilitate change, Anchoring safety through guidelines and Embracing COVID guidelines.CONCLUSION: A health crisis such as the COVID-19 pandemic can generate enabling elements for guideline implementation in healthcare, despite prevailing or new hindering components. The experience of guideline implementation during the COVID-19 pandemic can improve understanding of context aspects that can benefit organizations in everyday translation of evidence into practice.IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Recognizing what enabled guideline implementation in a health crisis can help first-line managers to identify local enabling context elements and processes. This can facilitate future guideline implementation.IMPACT: During the COVID-19 pandemic, the healthcare context and staff's motivation for guideline recognition and adoption changed. Resources and ways to bridge barriers in guideline implementation emerged, although specific challenges arose. Nursing managers can draw on experiences from the COVID-19 pandemic to support implementation of new evidence-based practices in the future.REPORTING METHOD: This study adheres to the EQUATOR guidelines by using Standards for Reporting Qualitative Research (SRQR). No Patient or Public Contribution.
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11. |
- Fjordkvist, Erika, 1985-, et al.
(författare)
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First-line managers’ experience of guideline implementation in orthopaedic nursing and rehabilitation : a qualitative study
- 2024
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Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: First-line managers have a unique role and potential in encouraging the use of evidence-based clinical practice guidelines (CPGs) and thus serve the provision of safe patient care. In acute and planned hospital care, effective yet safeguarded nursing procedures are a necessity. Little is currently known about how first-line managers engage in supporting the adoption of evidence-based nursing care and about what barriers and enablers there are for implementation of CPGs in the orthopaedic care context.Purpose: To investigate first-line managers' experience of clinical practice guideline implementation in orthopaedic care.Methods: This qualitative interview study included 30 first-line nursing and rehabilitation managers in 17 orthopaedic units in Sweden. A deductive content analysis, with the Ottawa Model of Implementation Leadership as a guide, was employed.Results: To the first-line managers, any guideline implementation required them to balance contexts, including their outer context (signified by the upper-level management and decision-makers) and their inner context, including staff and patients in their unit(s). Acting in response to these contexts, the managers described navigating the organization and its terms and conditions; using relations-, change-, and task-oriented leadership, such as involving the staff; motivating the change by emphasizing the patient benefits; and procuring resources, such as time and training. Even though they knew from past experience what worked when implementing CPGs, the first-line managers often encountered barriers within the contexts that hampered successful implementation.Conclusions: Although first-line managers know how to effectively implement CPGs, an organization's terms and conditions can limit their opportunities to fully do so. Organizational awareness of what supports and hinders first-line managers to offer implementation leadership can enhance opportunities to alter behaviours and conditions for the benefit of CPG implementation.Trial registration: The study was registered as NCT04700969 with the U.S. National Institutes of Health Clinical Trials Registry on 8 January 2021.
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13. |
- Hiltbrunner, Stefanie, et al.
(författare)
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Urinary Exosomes from Bladder Cancer Patients Show a Residual Cancer Phenotype despite Complete Pathological Downstaging
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Invasive urinary bladder cancer shows high recurrence rates after cystectomy even with apparent complete downstaging at cystectomy. Exosomes are nano-sized vesicles important in cell-cell communication, which have been hypothesized to contribute to cancer dissemination and recurrence. The aim of this study was to investigate if pro-carcinogenic exosomes could be detected in urine from histologically downstaged bladder cancer patients. 13 Patients were included in this study. Paired ureter and urine samples from nine patients underwent mass spectrometry, while samples from the remaining patients were used for exosome characterization. At cystectomy, exosomes were isolated from bladder and ureter urine, whereafter quantitative proteome profiling was performed. Urinary exosomes clustered based on whether they came from the bladder, with tumour contact, or the ureters, without tumour contact, even though all came from completely downstaged patients. Proteins overexpressed in exosomes derived from bladder urine contained several oncogenes and were mainly associated with tumour metabolism pathways. Although patients were histologically tumour-free at cystectomy, the bladder urine contained exosomes with a carcinogenic metabolic profile. This suggests a continuous release of exosomes from the bladder, which may promote recurrence at distant sites through metabolic rewiring, even after apparent complete downstaging. These exosomes, coming from either undetected cancer cells or partly transformed cells, are likely to increase the risk of metastasis and encourages cystectomy even in completely downstaged patients.
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14. |
- Sköld, Patricia, et al.
(författare)
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Patient participation in orthopaedic care-a survey on hip surgery patients' preferences for and experiences of engagement in their health and healthcare
- 2024
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Ingår i: International Journal of Orthopaedic and Trauma Nursing. - : Elsevier. - 1878-1241 .- 1878-1292. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Quality in health services is increasingly associated with enabling patients to participate in their own health and healthcare by recognising their resources and needs. Despite a growing recognition as to whether such participation is enabled, little is known regarding opportunities for preference-based patient participation in orthopaedic care. AIMS: To investigate preference-based participation for patients in orthopaedic care due to hip surgery.METHODS: Patients across 17 Swedish orthopaedic units who had had hip surgery, due to hip fracture or osteoarthritis, January-April 2021 were invited to complete the validated 4Ps questionnaire. Of 1514 patients, 458 patients returned the questionnaire with reports on their preferences for and experiences of participation. Each of the 4Ps' 12 items were analysed separately using descriptive and comparative statistics.RESULTS: A complete match in preferences for, and experiences of, participation was achieved with variation between items for 41%-50% of the patients; if almost matches were included, this occurred for 57%-77% of the patients. Less participation than preferred was most common in terms of having had reciprocal communication, opportunities for partaking in planning, and in learning how to manage symptoms/issues. Hip fracture surgery was significantly associated with experiencing lower levels of participation than preferred.CONCLUSION: Though standardised care promotes efficient hip surgery care, our study suggests a need for more person-centred opportunities to engage. A discrepancy was noted between patients' resources and preparation for their participation in and beyond the hip surgery process, particularly for self-care activities, calling for better use of nursing resources. ID: NCT04700969 with the U.S National Institutes of Health Clinical Registry.
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15. |
- Winberg, Madeleine, et al.
(författare)
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Adherence to evidence-based guidelines for prevention of urinary retention in hip surgery patients : A multicentre observational study
- 2024
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Ingår i: International Journal for Quality in Health Care. - : Pergamon Press. - 1353-4505 .- 1464-3677. ; 36:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary retention is a healthcare complication putting patients at risk of unnecessary suffering and harm. Orthopaedic patients are known to face an increased such risk, calling for evidence-based preoperative assessment and corresponding measures to prevent bladder problems. The aim of this study was to evaluate healthcare professionals' adherence to risk assessment guidelines for urinary retention in hip surgery patients.METHODS: This was an observational study from January 2021 to April 2021 with a descriptive and comparative design, triangulating three data sources. 1) Medical records for 1382 hip surgery patients across 17 hospitals in Sweden were reviewed for preoperative risk assessments for urinary retention and voiding-related variables at discharge. 2) The patients completed a survey regarding postoperative lower urinary tract symptoms, and 3) data was extracted from a national quality registry regarding type of surgery, preoperative physical status, and perioperative urinary complications. Group differences were analysed with Chi-square/ Fisher's exact test, t-test, Wilcoxon rank sum test, or Mann-Whitney U-test. Logistic regression was used to analyse variables associated with completed risk assessments for urinary retention.RESULTS: Of all study participants, 23.4% (n =323) had a preoperative documented risk assessment of urinary retention. Whether a risk assessment was performed was significantly associated with acute surgery (OR 3.56, 95% CI 2.48-5.12) and undergoing surgery at an academic hospital (OR 4.59, 95% CI 2.68-7.85). Acute patients were more often affected by urinary retention and had bladder issues and/or an indwelling catheter at discharge. More than every tenth patient (11. 9 %, n =53) completing the survey experienced intensified bladder problems after their hip surgery.CONCLUSION: The study shows a lack of adherence to risk assessment for urinary retention according to evidence-based guidelines, which negatively affects quality of care and patient safety.
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- Winberg, Madeleine, 1979-
(författare)
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Evidensbaserad blåsövervakning vid ortopedisk vård : Patienters erfarenheter och personals följsamhet till riskbedömning vid höftkirurgi
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hip surgery, a common healthcare procedure in Sweden and worldwide, is like other surgical procedures associated with risks of complications, such as urinary retention. Urinary retention is prompted by several factors experienced by the orthopaedic patient, such as pain, bed rest, medication (opioids, anaesthesia) and intravenous treatment with fluids. To prevent urinary retention or other voiding complications, there are evidence-based guidelines, supporting safe clinical care and averting unnecessary care injuries. Prior studies indicate that these guidelines are neither fully known nor used by orthopaedic staff, but bladder distension is still one of the most common adverse events in Swedish orthopaedic care. This licentiate thesis represents two studies, constituted by baseline data from 17 orthopaedic units in the Onset PrevenTIon of urinary retention in Orthopaedic Nursing and rehabilitation (OPTION) trial. Aim: The overall aim was to explore patients’ experiences of bladder care and voiding issues due to hip surgery and to evaluate staffs’ adherence to risk assessment for urinary retention according to evidence-based guide-lines. Design and method: Study I had a descriptive design and data was analysed using inductive content analysis. Study II was an observational study analysed with descriptive and comparative statistics, and logistic regressions. Findings: Patients experienced that bladder care and monitoring seemed important, although the reason was not fully explained to them, nor the related risk between hip surgery and urinary retention. Those experiencing bladder issues postoperatively managed and sought care on their own, not associating such events with their hip surgery. The bladder issues were described as negatively affecting daily life. Documentation in medical records (n=1382) indicated low adherence to recommended risk assessment for urinary retention (23.4%), and performed assessment was significantly associated with acute surgery or being treated at an academic hospital. Acute patients experienced urinary retention or other bladder issues more frequently, and among those patients completing a survey (n=447), 11.9% reported increased bladder issues after surgery. Conclusions: With a lack of communication with patients about bladder care, and limited adherence to risk assessment for urinary retention, further efforts to reinforce guideline implementation are needed. This should include a more patient-centred approach in the attempts to provide better, safer and more equal care.
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18. |
- Winberg, Madeleine, 1979-, et al.
(författare)
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Patients’ experiences of urinary retention and bladder care : A qualitative study in orthopaedic care
- 2023
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Ingår i: International Journal of Orthopaedic and Trauma Nursing. - : Elsevier. - 1878-1241 .- 1878-1292. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- Background: Urinary retention is a common complication associated with hip surgery. There are easily available, evidence-based clinical practice guidelines prescribing how to prevent both urinary retention and other voiding issues, by means of bladder monitoring and risk assessments. A detected lack of adherence to such guidelines increases risks for unnecessary suffering among patients but a greater understanding of patients’ experiences can benefit tailored interventions to address quality and safety gaps in orthopaedic nursing and rehabilitation.Purpose: The aim was to describe patients’ experiences of urinary retention, bladder issues, and bladder care in orthopaedic care due to hip surgery.Method: This was a qualitative study with a descriptive design: content analysis with an inductive approach was applied to interviews (n = 32) and survey free-text responses (n = 122) across 17 orthopaedic units in Sweden.Results: The patients had received no or limited details for the recurrent bladder care interventions (such as bladder scans and prompted voiding) while at the hospital. They relied on the staff for safe procedures but were left to themselves to manage and comprehend prevailing bladder issues. Despite the patients’ experiences of bladder issues or the risk of urinary retention postoperatively, the link to hip surgery remained unknown to the patients, leaving them searching for self-management strategies and further care.Conclusions: Patients’ perspectives on bladder care, urinary retention and bladder issues can serve as a means for increased understanding of procedures and issues, reinforcing improved implementation of guidelines, including person-centred information. Safer bladder procedures imply further patient engagement, highlighted in guidelines.
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