Patrickkorsholm5922

Conclusions The analysed randomised CTs were conducted in accordance with Good clinical practice with low risk of bias across domains. GC376 Only one CT was identified with some concerns of bias due to lack of information regarding the randomisation process and changes in protocol.Objective The objective of this paper is to determine an upper price limit for an orphan drug by taken a broader perspective and, including also other monetary and non-monetary values for the society. Methods This model is based on the expected free cash flows and the required minimum rate of return for the investor. In addition we calculated an innovation premium resulting from cost savings due to the substitution effect and the monetary gain in QALYs of a new medicine. We selected Spinraza®, a first in class drug with only best supportive care as comparator, and Perjeta®, a first in class drug with already an actual treatment as comparator. Results The results show that Spinraza® leads to an innovation premium of € 78,966 and Perjeta® shows an innovation premium of € 4,388, because there were no cost savings. The analyses show the outcomes are sensitive to discount rate for QALYs. Conclusion The break-even price from only an investor perspective may not reflect the value of drug from a broader perspective. This study shows drug prices based on an innovation premium may be more representative of the actual value of innovation for the society.Adaptive clinical trials are underway to determine the efficacy of potential therapies for COVID-19, with flexibility to include emerging therapies if there is sufficient preclinical evidence for their potential utility. In silico screening of connectivity maps, which link gene expression profiles to libraries of perturbagens, may facilitate the identification of such emerging therapies. The L1000 Connectivity Map is built from samples of transcripts taken from gene expression profiles of cells in various experimental conditions followed by computational inferences of the remainder of the transcriptome. Searching the L1000 Connectivity Map for modulators of a protease that facilitates coronavirus infection identifies plausible candidate drugs for repurposing as antiviral agents against SARS-CoV-2 following further investigation.The novel coronavirus SARS-CoV-2 is damaging the world's social and economic fabrics seriously. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-β, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.Clinical practice guidelines, such as those focusing on traumatic stress treatment, can play an important role in promoting inclusion and equity. Based on a review of 14 international trauma treatment guidance documents that explicitly mentioned children, we reflect on two areas in which these guidelines can become more inclusive and equitable; a) representation of children's cultural background and b) children's opportunity to have their voice heard. While a few guidelines mentioned that treatment should be tailored to children's cultural needs, there was little guidance on how this could be done. Moreover, there still appears to be a strong white Western lens across all stages of producing and evaluating the international evidence base. The available documentation also suggested that no young people under the age of 18 had been consulted in the guideline development processes. To contribute to inclusion and equity, we suggest five elements for future national guideline development endeavours. Promoting research and guideline development with, by, and for currently under-represented communities should be a high priority for our field. Our national, regional and global professional associations are in an excellent position to (continue to) stimulate conversation and action in this domain.Background Childhood sexual abuse (CSA) is a well-established risk factor for non-suicidal self-injury (NSSI) and suicide attempts (SA); still few studies have examined predictors of individual differences in NSSI/SA amongst CSA survivors. Objective To examine predictors of NSSI and SA among adult CSA-survivors. Methods In a sample of 516, primarily female adult CSA-survivors recruited from support centres for sexual abuse survivors in Norway, we examined the role of abuse/perpetrator characteristics, and the degree/severity of exposure to other types of childhood maltreatment (cumulative childhood maltreatment; CCM), as predictors of lifetime NSSI and SA. In a subsample of 138 individuals responding to follow-up waves two- and four years later, these same distal factors, as well as previous NSSI and proximal factors in the form of symptoms of mental health disorders (posttraumatic stress, anxiety, depression, sleep disturbances, and eating disorders), relational problems, and perceived social support, were eors.The present systematic review examined post-migration variables impacting upon mental health outcomes among asylum-seeking and refugee populations in Europe. It focuses on the effects of post-settlement stressors (including length of asylum process and duration of stay, residency status and social integration) and their impact upon post-traumatic stress disorder, anxiety and depression. Twenty-two studies were reviewed in this study. Length of asylum process and duration of stay was found to be the most frequently cited factor for mental health difficulties in 9 out of 22 studies. Contrary to expectation, residency or legal status was posited as a marker for other explanatory variables, including loneliness, discrimination and communication or language problems, rather than being an explanatory variable itself. However, in line with previous findings and as hypothesised in this review, there were statistically significant correlations found between family life, family separation and mental health outcomes.The oral cavity, as the entry point to the body, may play a critical role in the pathogenesis of SARS-CoV-2 infection that has caused a global outbreak of the coronavirus disease 2019 (COVID-19). Available data indicate that the oral cavity may be an active site of infection and an important reservoir of SARS-CoV-2. Considering that the oral surfaces are colonized by a diverse microbial community, it is likely that viruses have interactions with the host microbiota. Patients infected by SARS-CoV-2 may have alterations in the oral and gut microbiota, while oral species have been found in the lung of COVID-19 patients. Furthermore, interactions between the oral, lung, and gut microbiomes appear to occur dynamically whereby a dysbiotic oral microbial community could influence respiratory and gastrointestinal diseases. However, it is unclear whether SARS-CoV-2 infection can alter the local homeostasis of the resident microbiota, actively cause dysbiosis, or influence cross-body sites interactions. Here, we provide a conceptual framework on the potential impact of SARS-CoV-2 oral infection on the local and distant microbiomes across the respiratory and gastrointestinal tracts ('oral-tract axes'), which remains largely unexplored. Studies in this area could further elucidate the pathogenic mechanism of SARS-CoV-2 and the course of infection as well as the clinical symptoms of COVID-19 across different sites in the human host.[This corrects the article DOI 10.1080/20002297.2020.1798044.].

Acute tonsillitis is a very common medical condition. Despite different methods of detection, all tests are based on GAS sampling using a throat swab. However, obtaining the swab can elicit vomiting and is often accompanied by fear and apprehension in children. The aim of this study was to find a non-invasive method for the detection of GAS pharyngitis.

A classic throat swab was obtained for culture, and a saliva sample was taken from 100 subjects recruited from Meuhedet Health Care Organization clinic. Real time PCR was performed to detect GASdnaseBspecific gene in the saliva samples.

56% of the throat cultures and 48% of the PCR samples were positive for GAS. The overall sensitivity and specificity of the saliva PCR method was 79% and 91% respectively; NPV and PPV were 77% and 92% respectively. When excluding patients who presented on the first day of fever, sensitivity and specificity increased to 90% and 100% respectively. No other anamnestic or clinical findings increased the yield of the test.

Saliva-based PCR amplification of GAS DNA method is effective in detection of GAS pharyngitis. Further studies are needed to achieve detection rates to replace the traditional throat swab-based approach.

Saliva-based PCR amplification of GAS DNA method is effective in detection of GAS pharyngitis. Further studies are needed to achieve detection rates to replace the traditional throat swab-based approach.[This corrects the article DOI 10.1080/20002297.2019.1644111.].[This corrects the article DOI 10.1080/20002297.2019.1688449.].

Immune checkpoint inhibitors (ICIs) are novel therapeutic agents used for various types of cancer. ICIs have revolutionized cancer treatment and improved clinical outcomes among cancer patients. However, immune-related adverse effects of ICI therapy are common. Cardiovascular immune-related adverse events (irAEs) are rare but potentially life-threatening complications.

To estimate the incidence of cardiovascular irAEs among patients undergoing ICI therapy for various malignancies.

We conducted this systematic review and meta-analysis by searching PubMed, Cochrane CENTRAL, Web of Science, and SCOPUS databases for relevant interventional trials reporting cardiovascular irAEs. We performed a single-arm meta-analysis using OpenMeta [Analyst] software of the following outcomes Myocarditis, pericardial effusion, heart failure, cardiomyopathy, atrial fibrillation, myocardial infarction, and cardiac arrest. We assessed the heterogeneity using the

test and managed to solve it with Cochrane's leave-one-out method.