Molecular characterization of highly pathogenic H5N1 avian influenza viruses isolated in Sweden in 2006

<p>Abstract</p> <p>Background</p> <p>The analysis of the nonstructural (NS) gene of the highly pathogenic (HP) H5N1 avian influenza viruses (AIV) isolated in Sweden early 2006 indicated the co-circulation of two sub-lineages of these viruses at that time. In order to complete the information on their genetic features and relation to other HP H5N1 AIVs the seven additional genes of twelve Swedish isolates were amplified in full length, sequenced, and characterized.</p> <p>Results</p> <p>The presence of two sub-lineages of HP H5N1 AIVs in Sweden in 2006 was further confirmed by the phylogenetic analysis of approximately the 95% of the genome of twelve isolates that were selected on the base of differences in geographic location, timing and animal species of origin. Ten of the analyzed viruses belonged to sub-clade 2.2.2. and grouped together with German and Danish isolates, while two 2.2.1. sub-clade viruses formed a cluster with isolates of Egyptian, Italian, Slovenian, and Nigerian origin. The revealed amino acid differences between the two sub-groups of Swedish viruses affected the predicted antigenicity of the surface glycoproteins, haemagglutinin and neuraminidase, rather than the nucleoprotein, polymerase basic protein 2, and polymerase acidic protein, the main targets of the cellular immune responses. The distinctive characteristics between members of the two subgroups were identified and described.</p> <p>Conclusion</p> <p>The comprehensive genetic characterization of HP H5N1 AIVs isolated in Sweden during the spring of 2006 is reported. Our data support previous findings on the coincidental spread of multiple sub-lineage H5N1 HPAIVs via migrating aquatic birds to large distance from their origin. The detection of 2.2.1. sub-clade viruses in Sweden adds further data regarding their spread in the North of Europe in 2006. The close genetic relationship of Swedish isolates sub-clade 2.2.2. to the contemporary German and Danish isolates supports the proposition of the introduction and spread of a single variant of 2.2.2. sub-clade H5N1 avian influenza viruses in the Baltic region. The presented findings underline the importance of whole genome analysis.</p

Daily Sampling of an HIV-1 Patient with Slowly Progressing Disease Displays Persistence of Multiple env Subpopulations Consistent with Neutrality

The molecular evolution of HIV-1 is characterized by frequent substitutions, indels and recombination events. In addition, a HIV-1 population may adapt through frequency changes of its variants. To reveal such population dynamics we analyzed HIV-1 subpopulation frequencies in an untreated patient with stable, low plasma HIV-1 RNA levels and close to normal CD4+ T-cell levels. The patient was intensively sampled during a 32-day period as well as approximately 1.5 years before and after this period (days −664, 1, 2, 3, 11, 18, 25, 32 and 522). 77 sequences of HIV-1 env (approximately 3100 nucleotides) were obtained from plasma by limiting dilution with 7–11 sequences per time point, except day −664. Phylogenetic analysis using maximum likelihood methods showed that the sequences clustered in six distinct subpopulations. We devised a method that took into account the relatively coarse sampling of the population. Data from days 1 through 32 were consistent with constant within-patient subpopulation frequencies. However, over longer time periods, i.e. between days 1…32 and 522, there were significant changes in subpopulation frequencies, which were consistent with evolutionarily neutral fluctuations. We found no clear signal of natural selection within the subpopulations over the study period, but positive selection was evident on the long branches that connected the subpopulations, which corresponds to >3 years as the subpopulations already were established when we started the study. Thus, selective forces may have been involved when the subpopulations were established. Genetic drift within subpopulations caused by de novo substitutions could be resolved after approximately one month. Overall, we conclude that subpopulation frequencies within this patient changed significantly over a time period of 1.5 years, but that this does not imply directional or balancing selection. We show that the short-term evolution we study here is likely representative for many patients of slow and normal disease progression

Effectiveness of specialized rehabilitation after mild traumatic brain injury : A systematic review and meta-Analysis

Objective: To determine the effectiveness of specialized rehabilitation in adults with prolonged symptoms, or risk of prolonged symptoms, following mild traumatic brain injury. Data sources: Randomized controlled trials or nonrandomized controlled studies published between 1 Jan 2000 and 10 Mar 2019 in Cochrane Controlled Register of Trials, PubMed, EMBASE, CINAHL or PsycINFO. Meta-Analyses were performed for studies of similar interventions when identical or comparable outcomes were reported. Study selection and data extraction: Screening, data extraction, and risk of bias assessment were carried out by 2 independent researchers. Quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Data synthesis: A total of 9 studies were identified, which were divided into 3 subgroups. Results from meta-Analyses implied that problem-solving therapy and cognitive behavioural therapy reduce residual symptoms, improve psychological functioning, decrease depression, increase activity and participation, and improve quality of life, compared with usual care. The meta-Analyses also suggested that specialized interdisciplinary rehabilitation reduces residual symptoms. Conclusion: Persons with mild traumatic brain injury who are at risk of, or who experience, prolonged symptoms should be considered for specialist treatment, as they may experience positive effects from cognitive behavioural therapy, problem-solving therapy, or interdisciplinary team rehabilitation. Further research is required to strengthen the evidence

Appendix e-2 Extracted study data

Included studies and extracted study dat

Appendix e-1 Search strategy

Search strategy for Cochrane Library, Embase, and PubMed, 10 November 201

Appendix e-2 Extracted study data

Included studies and extracted study dat

Treatment of provoked vulvodynia : A systematic review

Background: Treatment recommendations for provoked vulvodynia (PVD) are based on clinical experiences and there is a need for systematically summarizing the controlled trials in this field. Aim: To provide an overview of randomized controlled trials and non-randomized studies of intervention for PVD, and to assess the certainty of the scientific evidence, in order to advance treatment guidelines. Data Sources: The search was conducted in CINAHL (EBSCO), Cochrane Library, Embase (Embase.com), Ovid MEDLINE, PsycINFO (EBSCO) and Scopus. Databases were searched from January 1, 1990 to January 29, 2021. Study Eligibility Criteria: Population: Premenopausal women with PVD. Interventions: Pharmacological, surgical, psychosocial and physiotherapy, either alone or as combined/team-based interventions. Control: No treatment, waiting-list, placebo or other defined treatment. Outcomes: Pain during intercourse, pain upon pressure or touch of the vaginal opening, sexual function/satisfaction, quality of life, psychological distress, adverse events and complications. Study design: Randomized controlled trials and non-randomized studies of interventions with a control group. Study Appraisal and Synthesis Methods: 2 reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias using established tools. The results from each intervention were summarized. Studies were synthesized using a narrative approach, as meta-analyses were not considered appropriate. For each outcome, we assessed the certainty of evidence using grading of recommendations assessment, development, and evaluation (GRADE). Results: Most results of the evaluated studies in this systematic review were found to have very low certainty of evidence, which means that we are unable to draw any conclusions about effects of the interventions. Multimodal physiotherapy compared with lidocaine treatment was the only intervention with some evidential support (low certainty of evidence for significant treatment effects favoring physiotherapy). It was not possible to perform meta-analyses due to a heterogeneity in interventions and comparisons. In addition, there was a heterogeneity in outcome measures, which underlines the need to establish joint core outcome sets. Clinical Implications: Our result underscores the need of stringent trials and defined core outcome sets for PVD. Strength and Limitations: Standard procedures for systematic reviews and the Population Intervention Comparison Outcome model for clinical questions were used. The strict eligibility criteria resulted in limited number of studies which might have resulted in a loss of important information. Conclusion: This systematic review underlines the need for more methodologically stringent trials on interventions for PVD, particularly for multimodal treatments approaches. For future research, there is a demand for joint core outcome sets

Brister i rehabilitering för vuxna med traumatisk hjärnskada

The Swedish Agency for Health Technology Assessment and Assessment of Social Services has evaluated quantitative and qualitative research regarding rehabilitation for persons with traumatic brain injury (TBI) through systematic reviews. The results indicate that specialized brain injury rehabilitation for persons with post-concussion symptoms after mild TBI results in improved health, when compared to usual care (results with low certainty according to GRADE). As few high-quality studies were identified, it was not possible to assess the effects of vocational rehabilitation, rehabilitation with case management/coordinator, residential living or specialized brain rehabilitation for persons with moderate to severe TBI. A synthesis of qualitative studies showed that persons with TBI experience insufficient coordination of health services and access to rehabilitation (results with low to moderate confidence according to CERQual).SBU:s utvärdering visar att det behövs fler välgjorda forskningsstudier om sammanhållen rehabilitering för vuxna med traumatisk hjärnskada.  Sammanvägd forskning indikerar att personer med restsymtom efter lätt traumatisk hjärnskada kan få förbättrad hälsa om de får specialiserad hjärnskaderehabilitering i stället för sedvanlig vård. Resultatens tillförlitlighet är dock låg. Det går inte att bedöma effekterna av arbetslivsinriktad rehabilitering, rehabilitering med samordnare, särskilda boendeformer eller specialiserad hjärnskaderehabilitering för personer med medelsvår till svår traumatisk hjärnskada.  Kvalitativ forskning visar att personer med traumatisk hjärnskada upplever brister gällande samordning och tillgänglighet till rehabilitering och att närstående utgör ett viktigt stöd.English title: Traumatic brain injury rehabilitation - assessment of quantitative and qualitative research</p

Brister i rehabilitering för vuxna med traumatisk hjärnskada

The Swedish Agency for Health Technology Assessment and Assessment of Social Services has evaluated quantitative and qualitative research regarding rehabilitation for persons with traumatic brain injury (TBI) through systematic reviews. The results indicate that specialized brain injury rehabilitation for persons with post-concussion symptoms after mild TBI results in improved health, when compared to usual care (results with low certainty according to GRADE). As few high-quality studies were identified, it was not possible to assess the effects of vocational rehabilitation, rehabilitation with case management/coordinator, residential living or specialized brain rehabilitation for persons with moderate to severe TBI. A synthesis of qualitative studies showed that persons with TBI experience insufficient coordination of health services and access to rehabilitation (results with low to moderate confidence according to CERQual).SBU:s utvärdering visar att det behövs fler välgjorda forskningsstudier om sammanhållen rehabilitering för vuxna med traumatisk hjärnskada.  Sammanvägd forskning indikerar att personer med restsymtom efter lätt traumatisk hjärnskada kan få förbättrad hälsa om de får specialiserad hjärnskaderehabilitering i stället för sedvanlig vård. Resultatens tillförlitlighet är dock låg. Det går inte att bedöma effekterna av arbetslivsinriktad rehabilitering, rehabilitering med samordnare, särskilda boendeformer eller specialiserad hjärnskaderehabilitering för personer med medelsvår till svår traumatisk hjärnskada.  Kvalitativ forskning visar att personer med traumatisk hjärnskada upplever brister gällande samordning och tillgänglighet till rehabilitering och att närstående utgör ett viktigt stöd.English title: Traumatic brain injury rehabilitation - assessment of quantitative and qualitative research</p