| 1. |
- Novak, Iona, et al.
(författare)
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Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy : Advances in Diagnosis and Treatment
- 2017
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 171:9, s. 897-907
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Forskningsöversikt (refereegranskat)abstract
- Importance: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age.Objectives: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function.Evidence Review: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument.Findings: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence.Conclusions and Relevance: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.
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| 2. |
- Warfvinge, Rebecca, et al.
(författare)
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Single-cell molecular analysis defines therapy response and immunophenotype of stem cell subpopulations in CML
- 2017
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:17, s. 2384-2394
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Tidskriftsartikel (refereegranskat)abstract
- Understanding leukemia heterogeneity is critical for the development of curative treatments as the failure to eliminate therapy-persistent leukemic stem cells (LSCs) may result in disease relapse. Here we have combined high-throughput immunopheno-typic screens with large-scale single-cell gene expression analysis to define the heterogeneity within the LSC population in chronic phase chronic myeloid leukemia (CML) patients at diagnosis and following conventional tyrosine kinase inhibitor (TKI) treatment. Our results reveal substantial heterogeneity within the putative LSC population in CML at diagnosis and demonstrate differences in response to subsequent TKI treatment between distinct subpopulations. Importantly, LSC subpopulations with myeloid and proliferative molecular signatures are proportionally reduced at a higher extent in response to TKI therapy compared with subfractions displaying primitive and quiescent signatures. Additionally, cell surface expression of the CML stem cell markers CD25, CD26, and IL1RAP is high in all subpopulations at diagnosis but downregulated and unevenly distributed across subpopulations in response to TKI treatment. The most TKI-insensitive cells of the LSC compartment can be captured within the CD45RA(-) fraction and further defined as positive for CD26 in combination with an aberrant lack of cKIT expression. Together, our results expose a considerable heterogeneity of the CML stem cell population and propose a Lin(-) CD34(+) CD38(-/low) CD45RA(-) cKIT(-) CD26(+) population as a potential therapeutic target for improved therapy response.
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| 3. |
- Borgström, Fredrik, et al.
(författare)
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Fragility fractures in Europe: burden, management and opportunities.
- 2020
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Ingår i: Archives of osteoporosis. - : Springer Science and Business Media LLC. - 1862-3514 .- 1862-3522. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years.Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6).A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric.Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 individuals age 50years or more were estimated at 21years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible individuals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men; an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided.Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are appropriately assessed and treated.
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| 4. |
- Börjesson, Stefan, 1979-, et al.
(författare)
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Detection of an IMI-2 carbapenemase-producing Enterobacter asburiae at a Swedish feed mill
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Occurrence of multidrug resistant Enterobacteriaceae in livestock is of concern as they can spread to humans. A potential introduction route for these bacteria to livestock could be animal feed. We therefore wanted to identify if Escherichia spp., Enterobacter spp., Klebsiella spp., or Raoutella spp. with transferable resistance to extended spectrum cephalosporins, carbapenems or colistin could be detected in the environment at feed mills in Sweden. A second aim was to compare detected isolates to previous described isolates from humans and animals in Sweden to establish relatedness which could indicate a potential transmission between sectors and feed mills as a source for antibiotic resistant bacteria. However, no isolates with transferable resistance to extended-cephalosporins or colistin could be identified, but one isolate belonging to the Enterobacter cloacae complex was shown to be carbapenem-resistant and showing carbapenemase-activity. Based on sequencing by both short-read Illumina and long-read Oxford Nanopore MinIon technologies it was shown that this isolate was an E. asburiae carrying a bla IMI-2 gene on a 216 Kbp plasmid, designated pSB89A/IMI-2, and contained the plasmid replicons IncFII, IncFIB, and a third replicon showing highest similarity to the IncFII(Yp). In addition, the plasmid contained genes for various functions such as plasmid segregation and stability, plasmid transfer and arsenical transport, but no additional antibiotic resistance genes. This isolate and the pSB89A/IMI-2 was compared to three human clinical isolates positive for bla IMI-2 available from the Swedish antibiotic monitoring program Swedres. It was shown that one of the human isolates carried a plasmid similar with regards to gene content to the pSB89A/IMI-2 except for the plasmid transfer system, but that the order of genes was different. The pSB89A/IMI-2 did however share the same transfer system as the bla IMI-2 carrying plasmids from the other two human isolates. The pSB89A/IMI-2 was also compared to previously published plasmids carrying bla IMI-2, but no identical plasmids could be identified. However, most shared part of the plasmid transfer system and DNA replication genes, and the bla IMI-2 gene was located next the transcription regulator imiR. The IS3-family insertion element downstream of imiR in the pSB89A was also related to the IS elements in other bla IMI-carrying plasmids.
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| 5. |
- Cable, Jennifer, et al.
(författare)
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Progress in vaccine development for infectious diseases : a Keystone Symposia report
- 2023
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Ingår i: Annals of the New York Academy of Sciences. - : John Wiley & Sons. - 0077-8923 .- 1749-6632. ; 1524:1, s. 65-86
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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| 6. |
- Christmas, Matthew, et al.
(författare)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 7. |
- Cunningham, Janet, et al.
(författare)
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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms
- 2022
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
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| 8. |
- Forsell, Mattias N. E., et al.
(författare)
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Regulation of subunit-specific germinal center B cell responses to the HIV-1 envelope glycoproteins by antibody-mediated feedback
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 8:JUN
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of germinal center (GC) B cell responses to single epitopes is well investigated. How monoclonal B cells are regulated within the polyclonal B cell response to protein antigens is less so. Here, we investigate the primary GC B cell response after injection of mice with HIV-1 envelope glycoproteins. We demonstrate that single GCs are seeded by a diverse number of B cell clones shortly after a single immunization and that the presence of Env-specific antibodies can inhibit the development of early GC B cells. Importantly, the suppression was dependent on the GC B cells and the infused antibodies to target the same subunit of the injected HIV-1 envelope glycoproteins. An affinity-dependent antibody feedback has previously been shown to regulate GC B cell development. Here, we propose that this antibody-based feedback acts on GC B cells only if they target the same or overlapping epitopes. This study provides important basic information of GC B cell regulation, and for future vaccine designs with aim to elicit neutralizing antibodies against HIV-1.
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| 9. |
- Gellerstedt, Linda, et al.
(författare)
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Nurses' experiences of hospitalised patients' sleep in Sweden : a qualitative study
- 2015
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 24:23/24, s. 3664-3673
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Tidskriftsartikel (refereegranskat)abstract
- AIMS AND OBJECTIVES:The aim was to describe nurses' experiences of patients' sleep at an emergency hospital and their perceptions of sleep-promoting interventions.BACKGROUND:Promotion of patients' sleep during hospital care is an important intervention for the nursing profession. To promote sleep and to initiate sleep-promoting interventions, nurses need basic knowledge about sleep and its physiology. Therefore, it is of importance to explore and expand knowledge about how nurses experience patients' sleep and how they perceive working with it while providing care.DESIGN:A qualitative descriptive design was used.METHODS:Data were collected from four focus groups and seven individual interviews. A total of twenty-two registered nurses participated. Data were analysed using a qualitative content analysis.RESULTS:Nurses expressed a desire and an ambition to work in ways that promote patients' sleep during hospitalisation. Nurses reported that health care services and emergency hospitals were not organised according to patients' perspective and needs. Furthermore, they did not have opportunities to work effectively to promote sleep according to the patients' wishes. Several nurses stated that they did not have sufficient knowledge about sleep and that they did the best they could under prevailing circumstances. Nurses emphasised the importance of sleep for patients and that it was an area that should be given far greater priority.CONCLUSIONS:The results indicate that nurses currently have insufficient knowledge about sleep and sleep-promoting interventions. These aspects of nursing is based on personal experience and common sense rather than being evidence based. Furthermore, sleep as a nursing topic needs to be developed and given more focus in order for nurses to be able to deliver high quality care at emergency hospitals.RELEVANCE TO CLINICAL PRACTICE:Nurses require more knowledge and education to gain deeper understanding of sleep and to deliver evidence-based, high quality care.
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| 10. |
- Gellerstedt, Linda, et al.
(författare)
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Nursing care and management of patients' sleep during hospitalisation : a cross-sectional study
- 2019
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 28:19-20, s. 3400-3407
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To explore and describe how patients' sleep is addressed at acute-care hospitals in Sweden with regard to nursing care, management, and the development of knowledge in this area.BACKGROUND: Sleep is a basic human need and thus important for health and health maintenance. Patients describe sleeping in hospital as a stressor, and research shows that nurses tend to underestimate patients' perceived problems with sleep during hospitalization. How do nursing staff at acute hospitals address patients' sleep and the development of knowledge in this area?.DESIGN/METHOD: A cross-sectional descriptive study was conducted based on data collected through a web survey. Head nurses, registered nurses, nursing care developers, and local training supervisors at 36 randomized acute-care hospitals in Sweden were invited to participate. This study was executed and reported in accordance with SQUIRE 2.0.RESULTS: The results of the survey (53 responses from 19 wards at 15 acute-care hospitals) showed that no policy documents exist and no current training addresses sleep during hospital stay. All participants agreed that sleep should be considered a nursing topic and that it is important for hospitalized patients.CONCLUSION: Patients' sleep during hospitalization is undermanaged at acute-care hospitals. Nurses, health care managers, and organizations face challenges if they are to achieve better outcomes.RELEVANCE TO CLINICAL PRACTICE: This study shows that nurses do consider patients' sleep important and addressing sleep as part of nursing care. Future studies in the area should focus on what kinds of support and education are needed in the clinical context. This article is protected by copyright. All rights reserved.
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