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| 2. |
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| 3. |
- Li, X., et al.
(författare)
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Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC(4)E trial in 15 European countries
- 2023
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Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7598 .- 1618-7601. ; 24:6, s. 909-922
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Tidskriftsartikel (refereegranskat)abstract
- Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. Methods Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers' and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. Results The healthcare payers' expected ICERs of oseltamivir were euro22,459 per QALY gained in adults/adolescents and euro13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is euro8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged euro1-euro35 per patient). Conclusion Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers' perspective (if willingness-to-pay per QALY gained > euro22,459) and cost-saving in adults/adolescents from a societal perspective.
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| 4. |
- Butler, C. C., et al.
(författare)
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Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial
- 2020
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 395:10217, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- Background Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. Methods We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. Findings Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1.29, 95% Bayesian credible interval [BCrI] 1.20-1.39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1.13 to 1.72. The estimated absolute mean benefit from oseltamivir was 1.02 days (95% [BCrI] 0.74-1.31) overall, and in the prespecified subgroups, ranged from 0.70 (95% BCrI 0.30-1.20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3.20 (95% BCrI 1.00-5.50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. Interpretation Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 6. |
- Goossens, E, et al.
(författare)
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Fertility preservation in boys: recent developments and new insights †
- 2020
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Ingår i: Human reproduction open. - : Oxford University Press (OUP). - 2399-3529. ; 2020:3, s. hoaa016-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDInfertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility.OBJECTIVE AND RATIONALEWith this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss.SEARCH METHODSBased on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity.OUTCOMESSince the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation.LIMITATIONS, REASONS FOR CAUTIONThe review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention.WIDER IMPLICATIONSThe revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss.STUDY FUNDING/COMPETING INTEREST(S)The work was funded by ESHRE. None of the authors has a conflict of interest.
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| 7. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 8. |
- Hoste, M. E., et al.
(författare)
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The experiences of patients ill with COVID-19-like symptoms and the role of testing for SARS-CoV-2 in supporting them: A qualitative study in eight European countries during the first wave of the pandemic
- 2023
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Ingår i: European Journal of General Practice. - 1381-4788. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAccess to testing during the first wave of the COVID-19 pandemic was limited, impacting patients with COVID-19-like symptoms. Current qualitative studies have been limited to one country or were conducted outside Europe.ObjectivesTo explore - in eight European countries - the experiences of patients consulting in primary care with COVID-19-like symptoms during the first wave of the pandemic.MethodsSixty-six semi-structured interviews, informed by a topic guide, were conducted by telephone or in person between April and July 2020. Patients with COVID-19-like symptoms were purposively recruited in primary care sites in eight countries and sampled based on age, gender, and symptom presentation. Deductive and inductive thematic analysis techniques were used to develop a framework representing data across settings. Data adequacy was attained by collecting rich data.ResultsSeven themes were identified, which described the experiences of patients consulting. Two themes are reported in this manuscript describing the role of COVID-19 testing in this experience. Patients described significant distress due to their symptoms, especially those at higher risk of complications from COVID-19, and those with severe symptoms. Patients wanted access to testing to identify the cause of their illness and minimise the burden of managing uncertainty. Some patients testing positive for COVID-19 assumed they would be immune from future infection.ConclusionPatients experiencing novel and severe symptoms, particularly those with comorbidities, experienced a significant emotional and psychological burden due to concerns about COVID-19. Testing provided reassurance over health status and helped patients identify which guidance to follow. Testing positive for SARS-CoV-2 led to some patients thinking they were immune from future infection, thus influencing subsequent behaviour.
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| 9. |
- Ouchi, D., et al.
(författare)
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Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries
- 2022
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Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 39:3, s. 398-405
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Tidskriftsartikel (refereegranskat)abstract
- Lay Summary Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms. Background Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. Objective We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. Methods Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. Results A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 +/- 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). Conclusion Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.
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| 10. |
- Verheij, T. J., et al.
(författare)
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Clinical presentation, microbiological aetiology and disease course in patients with flu-like illness: A post hoc analysis of randomised controlled trial data
- 2022
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Ingår i: British Journal of General Practice. - 0960-1643. ; 72:716
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Tidskriftsartikel (refereegranskat)abstract
- Background There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. Aim To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. Design and setting Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. Method Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. Results Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. Conclusion Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-andsee policy in most of these patients with flu-like illness seems the best option. © 2022 Royal College of General Practitioners. All rights reserved.
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| 11. |
- Wanat, M., et al.
(författare)
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Patients’ and clinicians’ perspectives on the primary care consultations for acute respiratory infections during the first wave of the COVID-19 pandemic: an eight-country qualitative study in Europe
- 2022
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Ingår i: BJGP Open. - 2398-3795. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The impact of the COVID-19 pandemic on patients’ and clinicians’ perceptions of healthcare-seeking behaviour and delivery of care is unclear. The pandemic accelerated the use of remote care, and understanding its benefits and drawbacks may inform its implementation during current and future healthcare emergencies. Aim: To explore patients’ and primary care professionals’ (PCPs) experiences of primary care delivery in the first wave of the pandemic. Design & setting: Qualitative study using semi-structured interviews in primary care in eight European countries (England, Ireland, Belgium, the Netherlands, Greece, Poland, Sweden, and Germany). Method: A total of 146 interviews were conducted with 80 PCPs and 66 patients consulting for respiratory tract infection (RTI) symptoms, in eight European countries. Data were collected between April and July 2020, and analysed using thematic analysis. Results: It was found that patients accepted telemedicine when PCPs spent time to understand and address their concerns, but a minority preferred in-person consultations. PCPs felt that remote consultations created emotional distance between themselves and patients, and they reported having to manage diverse COVID-19-related medical and social concerns. Conclusion: Remote consultations for RTI symptoms may be acceptable long term if both groups are happy to use this format, but it is important that PCPs take time to address patients’ concerns and provide safety-netting advice.
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| 12. |
- Wanat, M., et al.
(författare)
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Supporting Primary Care Professionals to Stay in Work During the COVID-19 Pandemic: Views on Personal Risk and Access to Testing During the First Wave of Pandemic in Europe
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimising primary care professionals' (PCPs) risk of SARS-CoV-2 infection is crucial to ensure their safety as well as functioning health care system. PCPs' perspectives on the support they needed in the early stages of a public health crisis can inform future preparedness. Aim: To understand PCPs' experiences of providing care during the COVID-19 pandemic, with focus on personal risk from COVID-19 and testing. Design and Setting: Qualitative study using semi-structured interviews with PCPs in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece and Sweden, between April and July 2020. Method: Interviews were analysed using a combination of inductive and deductive thematic analysis techniques. Results: Eighty interviews were conducted, showing that PCPs tried to make sense of their risk of both contracting and severity of COVID-19 by assessing individual risk factors and perceived effectiveness of Personal Protective Equipment (PPE). They had limited access to PPE yet continued providing care as their "duty." Some PCPs felt that they were put in high-risk situations when patients or colleagues were not flagging symptoms of COVID-19. Not having access to testing in the initial stages of the pandemic was somewhat accepted but when available, was valued. Conclusion: Access to adequate PPE and testing, as well as training for staff and education for patients about the importance of ensuring staff safety is crucial. Given PCPs' varied response in how they appraised personal risk and their tolerance for working, PCPs may benefit from the autonomy in deciding how they want to work during health emergencies.
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| 13. |
- Wanat, M., et al.
(författare)
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Transformation of primary care during the COVID-19 pandemic: experiences of healthcare professionals in eight European countries
- 2021
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Ingår i: British Journal of General Practice. - : Royal College of General Practitioners. - 0960-1643 .- 1478-5242. ; 71:709
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Tidskriftsartikel (refereegranskat)abstract
- Background I'm Tian/care has a crucial role in responding to the COVID-19 pandemic as the first point of patient care and gatekeeper to secondary care. Qualitative studies exploring the experiences of healthcare professionals during the COVID-19 pandemic have mainly focused on secondary care. Aim To gain an understanding of the experiences of European primary care professionals (PCPs) working during the first peak of the COVID-19 pandemic. Design and setting An exploratory qualitative study, using semi structured interviews in primary care in England, Belgium, the Netherlands. Ireland. Germany, Poland, Greece, and Sweden, between April and July 7020. Method Interviews were audiorecorded, transcribed, and analysed using a combination of inductive and deductive thematic analysis techniques. Results Fighty interviews were conducted with PCPs. PCPs had to make their own decisions on how to rapidly transform services in relation to COVID-19 and non-COVID-19 care. Despite being overwhelmed with guidance. they often lacked access to practical training. Consequently. PCPs turned to their colleagues for moral support and information to try to quickly adjust to new ways of working, including remote care. arid to deal with uncertainty. Conclusion PCPs rapidly transformed primary care delivery despite a number of challenges. Representation of primary care at policy level and engagement with local primary care champions are needed to facilitate easy and coordinated access to practical information on how to adapt services, ongoing training, and access to appropriate mental health support services for PCPs. Preservation of autonomy and responsiveness of primary care are critical to preserve the ability for rapid transformation in any future crisis of care delivery.
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| 17. |
- Runge, N., et al.
(författare)
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The effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis - A systematic review with meta-analysis
- 2023
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Ingår i: SLEEP MEDICINE REVIEWS. - 1087-0792 .- 1532-2955. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- This systematic review aimed to systematically investigate the literature on the effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis. For that, seven databases were searched for relevant randomized controlled trials. After the searches, 36 studies investigating 2281 participants were included. Risk of bias assessments were done by two independent reviewers using the Cochrane Risk of Bias tool 2. Random-effects meta-analyses were performed, and the Grading of Recommendations Assessment, Development and Evaluation framework was used to judge the certainty of evidence. The evidence on benefits of exercise and physical activity programs on fatigue and sleep parameters in people with osteoarthritis and psoriatic arthritis was either lacking or inconclusive. There was very low to low certainty evidence for a slight benefit of exercise and physical activity programs on fatigue at short-term in people with ankylosing spondylitis and rheumatoid arthritis. However, the evidence was very uncertain for the medium- and long-term as well as for any sleep parameters. The results indicate that exercise and physical activity programs may offer some benefits on fatigue for people with arthritis in the short-term, although the best type of exercise remains uncertain. The available evidence on improvements in sleep was insufficient to draw strong conclusions.
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| 18. |
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| 19. |
- von Seth, J, et al.
(författare)
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Genomic insights into the conservation status of the world's last remaining Sumatran rhinoceros populations
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Small populations are often exposed to high inbreeding and mutational load that can increase the risk of extinction. The Sumatran rhinoceros was widespread in Southeast Asia, but is now restricted to small and isolated populations on Sumatra and Borneo, and most likely extinct on the Malay Peninsula. Here, we analyse 5 historical and 16 modern genomes from these populations to investigate the genomic consequences of the recent decline, such as increased inbreeding and mutational load. We find that the Malay Peninsula population experienced increased inbreeding shortly before extirpation, which possibly was accompanied by purging. The populations on Sumatra and Borneo instead show low inbreeding, but high mutational load. The currently small population sizes may thus in the near future lead to inbreeding depression. Moreover, we find little evidence for differences in local adaptation among populations, suggesting that future inbreeding depression could potentially be mitigated by assisted gene flow among populations.
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