| 1. |
- Müller, Kathrin, et al.
(författare)
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De novo mutations in SOD1 are a cause of ALS
- 2022
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 93, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The only identified cause of amyotrophic lateral sclerosis (ALS) are mutations in a number of genes found in familial cases but also in sporadic cases. De novo mutations occurring in a parental gonadal cell, in the zygote or postzygotic during embryonal development can result in an apparently sporadic/isolated case of ALS later in life. We searched for de novo mutations in SOD1 as a cause of ALS.Methods: We analysed peripheral-blood exome, genome and Sanger sequencing to identify deleterious mutations in SOD1 in 4000 ALS patients from Germany, South Korea and Sweden. Parental kinship was confirmed using highly polymorphic microsatellite markers across the genome. Medical genealogical and clinical data were reviewed and compared with the literature.Results: We identified four sporadic ALS cases with de novo mutations in SOD1. They aggregate in hot-spot codons earlier found mutated in familial cases. Their phenotypes match closely what has earlier been reported in familial cases with pathogenic mutations in SOD1. We also encountered familial cases where de novo mutational events in recent generations may have been involved.Conclusions: De novo mutations are a cause of sporadic ALS and may also be underpinning smaller families with few affected ALS cases. It was not possible to ascertain if the origin of the de novo mutations was parental germline, zygotic or postzygotic during embryonal development. All ALS patients should be offered genetic counselling and genetic screening, the challenges of variant interpretation do not outweigh the potential benefits including earlier confirmed diagnosis and possible bespoken therapy.Data availability statement: Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.
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| 2. |
- Nordin, Angelica, et al.
(författare)
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Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation : a large multinational screening study
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 18:3-4, s. 256-264
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Tidskriftsartikel (refereegranskat)abstract
- A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele. In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.
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| 3. |
- Akimoto, Chizuru, et al.
(författare)
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A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:6, s. 419-424
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Tidskriftsartikel (refereegranskat)abstract
- Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.
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| 4. |
- Andersson, Maria, 1969-, et al.
(författare)
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Moral Distress, Health and Intention to Leave: Critical Care Nurses’ Perceptions During COVID-19 Pandemic
- 2023
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Ingår i: Sage Open Nursing. - : SAGE Publications Inc.. - 2377-9608. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Moral distress increases the risk that critical care nurses will lose the ability to provide quality nursing care.Aims: To describe person-related conditions and perceptions of moral distress, health and intention to leave among critical care nurses in intensive care units, and to examine the relationship between person-related conditions, moral distress, health and intention to leave.Method: Cross-sectional, with 220 critical care nurses in 15 Swedish ICUs, and data gathered via a self-reported questionnaire.Results: Highest moral distress scores were reported in futile care and poor teamwork and 21% reported entertaining an intention to leave. Self-reported health was lower than before the COVID-19 pandemic and 4.1% reported pronounced exhaustion disorder. Self-reported health, reduced capacity to tolerate demands under time pressure, emotional instability or irritability, physical weakness, or being more easily fatigued and with decreased well-being were factors that had a relationship with futile care. Sleeping problems and intention to leave had a relationship with poor teamwork.Conclusions: Different strategies are needed to reduce moral distress and the leadership is crucial for managing crises such as the COVID-19 pandemic.
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| 5. |
- Andersson, Maria, et al.
(författare)
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The four domains of the person-centred practice framework from the perspective of critical care nurses in intensive care units during a pandemic
- 2023
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Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 78
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim was to describe the Person-Centred Practice Framework’s four domains (prerequisites, care environment, person-centred processes, and person-centred outcomes) through the perspectives of critical care nurses working in intensive care units during the second year of the COVID-19 pandemic. Furthermore, the aim was to investigate the relationships between prerequisites, care environment, person-centred processes, and person-centred outcomes. Design/methods: A cross-sectional study involving questionnaires. Prerequisites were measured using person- related conditions, the care environment by using the Person-Centred Climate Questionnaire–Staff version, the person-centred processes by using the Person-Centred Care Assessment Tool and person-centred outcomes were measured with one question about present health and well-being and by using Self-rated Exhaustion Disorder. Descriptive and analytic statistics were used. Data was collected from July 2021 to November 2021. Setting: Critical care nurses (n =217) working in 15 Swedish adult intensive care units. Results: Participants’ average length of experience in intensive care units was 14 years, and most participants experienced increased nursing care responsibilities. They perceived the climate as safe but had limitations in terms of its everydayness and community. Participants perceived the organisations both supported and hindered personalized care. Most participants experienced a variety of exhaustion symptoms, and their health had positive relationship with community. Conclusion: By showing how prerequisites, care environment, person-centred process influences critical care nurses’ health and well-being, organisations might identify aspects in the work environment that require targeted interventions to reach healthy workplaces. Implications for clinical practice: To preserve the health and well-being of critical care nurses and to flourish as humans in their professional roles, they need to interact with and form relationships with their colleagues, patients, and relatives. Organisations should have a person-centred approach for every individual in the workforce to harness each critical care nurses’ knowledge and skills for individuals to growth in their roles.
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| 6. |
- Andersson-Sköld, Yvonne, 1957-, et al.
(författare)
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Development of the SUNRA Tool to Improve Regional and Local Sustainability of the Transportation Sector
- 2022
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 14:18, s. 11275-
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Tidskriftsartikel (refereegranskat)abstract
- To fulfil the global sustainable development goals (SDGs), achieving sustainable development is becoming urgent, not least in the transportation sector. In response to this, the sustainability framework Sustainability National Road Administrations (SUNRA) was developed to contribute to improving the sustainability performance of national road administrations across Europe. In the present study, the framework has been tested, applied and further developed to be applicable for target setting and follow-up at the project level at both the Swedish Transport Administration (STA) and at municipal levels. The aim was a framework relevant for investment, re-investments, maintenance and operation projects and also to make it more user applicable. The study also investigated how the framework can contribute to sustainability, identified drivers and barriers for applying the framework and examined whether the framework can be applied and adapted to projects of different complexities. The adaptations and developments were done in collaboration between researchers and practitioners. The results show that the framework could easily be used and adapted for investment, re-investment, maintenance and operation projects in the planning stage, as well as for small municipal establishments, construction or reconstruction of residential areas and frequent maintenance. The framework contributes to increased awareness on sustainability, and it provides a common structure and transparency on how infrastructure project goals/targets are set and fulfilled. The framework can also be applied to follow the fulfilment of the goals/targets and thereby adapt the project to better fulfil the goals. Identified barriers include the lack of obligations and lack of experience in using sustainability frameworks.
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| 7. |
- Engström, Åsa, et al.
(författare)
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Institutional Constraints as an Obstacle for Prioritizing Nursing Interventions During the COVID-19 Pandemic—Critical Care Nurses’ Experiences
- 2022
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Ingår i: Sage Open Nursing. - : Sage Publications. - 2377-9608. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The demands of the pandemic such as staff shortages and limited resources combined with new guidelines regarding infection control may have required the prioritizing of nursing interventions.Objectives: The aim of this study was to describe critical care nurses’ experiences of prioritizing nursing interventions for patients with COVID-19 in intensive care units (ICUs) during the pandemic.Method: A qualitative descriptive study was gathered from open-ended questions included in a cross-sectional online questionnaire. Characteristics were presented using descriptive statistics, and open-ended questions were analyzed using qualitative content analysis with an inductive approach. The study was conducted in Sweden and focused on critical care nurses working in ICUs during spring 2021 and the second year of the COVID-19 pandemic.Results: During the COVID-19 pandemic, 87% of the critical care nurses had provided orientations for new co-workers, and 52% had supervised intensive care nursing students. In all, 70 answered the question of whether they had prioritized nursing care differently during the pandemic; 86% reported that they had and 14% had not. The qualitative analysis resulted in one theme, Institutional constraints as an obstacle for nursing interventions, with three categories: Prioritizing lifesaving interventions, Performing nursing interventions less frequently, and Not able to provide the nursing care I wish to provide.Conclusion: Institutional constraints as an obstacle for nursing interventions is the overall theme. It illustrates how critical care nurses have been forced to prioritize, thereby not being able to provide the nursing interventions they wanted to do provide, and it describes their feelings in this situation. The nurses need recovery and possibilities for reflection. The organization must also recover and not only return to how it was before the pandemic but also to learn from recent events and take actions to reduce the long-term effects on staffing.
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| 8. |
- Fredholm, Angelica, et al.
(författare)
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Learning in intensive care during the COVID-19 pandemic - postgraduate critical care nursing students’ experiences
- 2022
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Ingår i: International Journal of Medical Education. - : NLM (Medline). - 2042-6372. ; 13, s. 335-344
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study explored postgraduate critical care nursing students' experiences of learning in the ICU during the COVID-19 pandemic and to understand these experiences in relation to self-directed learning and professional development. Methods: An explorative qualitative design was used. Eight postgraduate critical care nursing students from two different universities were interviewed. Questions focused on learning, supervision, ethically difficult situations, issues regarding communication, as well as the impact of the pandemic on students' health. Interviews thematically analyzed, and further analyzed using a theoretical framework focusing self-directed learning and professional development containing the concepts of autonomy, authenticity, and attachment. Results: The result consists of three themes: 1) Attachment with subthemes Attachment to the patient, Attachment to family and friends, Attachment to the ICU-context, and Attachment to the clinical supervisor. 2) Authenticity with subthemes Experiencing a varying degree of authenticity, Clinical reasoning about how to prioritize care. 3) Autonomy with subthemes Being just a student - with limited responsibility, taking responsibility, and having worries regarding one's professional development. Conclusion: Findings show the need for participation in the ICU community of practice without the demands and responsibility of full participation. Students need to be given the opportunity to form a relationship with practice. For attachment, participation, and consequently professional development to take place, there is need for inviting students to be a part of the team even during such straining circumstances as an ongoing pandemic. These findings can advance the understanding of how to organize clinical education during future crisis such as a new pandemic.
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| 9. |
- Koch Frisén, Angelica, et al.
(författare)
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Prospective evaluation of 6895 groin hernia repairs in women
- 2005
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 92:12, s. 1553-1558
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 8 per cent of groin hernia repairs are performed in women, there is little published literature relating specifically to women. This study compared differences in outcome between women and men after groin hernia repair.Methods: Data collected prospectively in the Swedish Hernia Register between 1992 and 2003 were analysed, including 6895 groin hernia repairs in women and 83 753 in men.Results: A higher proportion of emergency operations was carried out in women (16.9 per cent) than men (5.0 per cent), leading to bowel resection in 16.6 and 5.6 per cent respectively. During reoperation femoral hernias were found in 41.6 per cent of the women who were diagnosed with a direct or indirect inguinal hernia at the primary operation. The corresponding proportion for men was 4.6 per cent. The hernia repair was not classified as a standard operation (e.g. Shouldice, Lichtenstein, Plug/Mesh, TAPP/TEP) in 38.2 per cent of women and 11.2 per cent of men. Women had a significantly higher risk of reoperation for recurrence than men, and techniques associated with the lowest risk for reoperation in men had the highest risk in women.Conclusion: A greater proportion of women than men require emergency groin hernia repair, with consequently higher rates of bowel resection, complications and death. Surgical techniques developed for use in men may put women at unnecessary risk. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.
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| 10. |
- Nordin, Angelica, et al.
(författare)
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Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:11, s. 3133-3142
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Tidskriftsartikel (refereegranskat)abstract
- A GGGGCC-repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasians. However, little is known about the variability of the GGGGCC expansion in different tissues and whether this correlates with the observed phenotype. Here, we used Southern blotting to estimate the size of hexanucleotide expansions in C9orf72 in neural and non-neural tissues from 18 autopsied ALS and FTD patients with repeat expansion in blood. Digitalization of the Southern blot images allowed comparison of repeat number, smear distribution and expansion band intensity between tissues and between patients. We found marked intra-individual variation of repeat number between tissues, whereas there was less variation within each tissue group. In two patients, the size variation between tissues was extreme, with repeat numbers below 100 in all studied non-neural tissues, whereas expansions in neural tissues were 20-40 times greater and in the same size range observed in neural tissues of the other 16 patients. The expansion pattern in different tissues could not distinguish between diagnostic groups and no correlation was found between expansion size in frontal lobe and occurrence of cognitive impairment. In ALS patients, a less number of repeats in the cerebellum and parietal lobe correlated with earlier age of onset and a larger number of repeats in the parietal lobe correlated with a more rapid progression. In 43 other individuals without repeat expansion in blood, we find that repeat sizes up to 15 are stable, as no size variation between blood, brain and spinal cord was found.
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