Wallerprince2774

Objective Our pharmacogenomic study evaluated the influence of the presence/absence of genetic variants of psoriasis-risk loci on the clinical response to secukinumab. Differences in the single-nucleotide polymorphism (SNP) pattern characterizing HLA-Cw6+ or HLA-Cw6- patient subpopulations, showing high or low responses to secukinumab, were also analyzed. Methods 417 SNPs were analyzed by Next-Generation Sequencing technology, in a cohort of 62 psoriatic patients and undergone secukinumab treatment. Univariate regression analysis was employed to examine the association between SNP and clinical response to secukinumab. Multivariate analysis was also performed to assess multivariate differences in SNP pattern of HLA-Cw6+ or HLA-Cw6- patients showing high or low responses to secukinumab. Results Eight SNPs in HLA-C and upstream region (rs13207315, rs6900444, rs12189871, rs12191877, rs4406273, and rs10484554), including HLA-Cw6 classical allele (rs1131118), and three in MICB-DT (rs9267325), DDX58 (rs34085293) and TYK2 (rs2304255) genes, associating with excellent response to secukinumab were identified. Importantly, rs34085293 or rs2304255 SNP status defined a subgroup of super-responder patients. We also found that HLA-Cw6+ and HLA-Cw6- patients carried out specific patterns of SNPs associating with different responses to secukinumab. Conclusion Assessment of HLA-Cw6, together with other allelic variants of genes, could be helpful to define patients which better benefit from anti-IL-17 therapy. Abbreviations PASI Psoriasis Area and Severity Index; SNP Single-Nucleotide Polymorphism Rs Reference SNP; PASI75 75% reduction in Psoriasis Area and Severity Index; PASI90 90% reduction in Psoriasis Area and Severity Index; PASI100 100% reduction in Psoriasis Area and Severity Index; NGS Next-Generation Sequencing; OR Odds Ratio; CAP Canonical Analysis of Principal coordinates; BMI Body Mass Index; LD Linkage Disequilibrium.Introduction Headache is the fifth most common reason to visit an emergency department (ED). In most of the cases, headache is benign and has a primary origin, with migraine as the most common diagnosis. Inappropriate use of ED for non-emergency conditions causes overcrowding, unnecessary testing, and increased medical costs.Areas covered All stages of headache management in ED, from the reasons to go there, the diagnosis that is made and the investigations necessary to make it, to get to the therapies administered and those prescribed at discharge, if there were any. Finally, the authors evaluated the habit of recommending medical follow-up and how often the headache is still present at discharge or returns within 24 hours.Expert Opinion Primary headaches are underdiagnosed, misdiagnosed, and the majority do not receive drug therapy either in ED or on discharge, and in cases where the therapy is prescribed is not specific. Increase the number of primary care medical services, spread the 'headaches culture' among GPs and ED doctors, the adoption of ICHD in the diagnostic protocols used in EDs and a fast referral to a headache center could decrease the inappropriate use of ED and improve the headache management in the emergency units.

Despite significant advances in treatment and prevention, graft-versus-host disease (GVHD) still represents the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Thus, considerable research efforts have been made to find and validate reliable biomarkers for diagnosis, prognosis, and risk stratification of GVHD.

In this review the most recent evidences on different types of biomarkers studied for GVHD, such as genetic, plasmatic, cellular markers, and those associated with microbiome, were summarized. A comprehensive search of peer-review literature was performed in PubMed including meta-analysis, preclinical and clinical trials, using the terms cellular and plasma biomarkers, graft-versus-host disease, cytokines, and allogeneic hematopoietic stem cell transplantation.

In the near future, several validated biomarkers will be available to help clinicians in the diagnosis of GVHD, the identification of patients at high risk of GVHD development and in patients' stratification according to its severity. Then, immunosuppressive treatment could be tailored to each patient's real needs. However, more efforts are needed to achieve this goal. Although most of the proposed biomarkers currently lack validation with large-scale clinical data, their study led to improved knowledge of the biological basis of GVHD, and ultimately to implementation of GHVD treatment.

In the near future, several validated biomarkers will be available to help clinicians in the diagnosis of GVHD, the identification of patients at high risk of GVHD development and in patients' stratification according to its severity. Then, immunosuppressive treatment could be tailored to each patient's real needs. However, more efforts are needed to achieve this goal. Although most of the proposed biomarkers currently lack validation with large-scale clinical data, their study led to improved knowledge of the biological basis of GVHD, and ultimately to implementation of GHVD treatment.Introduction Status epilepticus (SE) is a neurologic and medical emergency with significant related morbidity and mortality. Hepatic or renal dysfunction can considerably affect the pharmacokinetics of drugs used for SE through a variety of direct or indirect mechanisms. Areas Covered This review aims to focus on the therapeutic management of SE in patients with hepatic or renal impairment, highlighting drugs' selection and dose changes that may be necessary due to altered drug metabolism and excretion. The references for this review were identified by searches of PubMed and Google Scholar until May 2020. Expert opinion According to literature evidence and clinical experience, in patients with renal disease, the authors suggest considering lorazepam as the drug of choice in pre-hospital and intra-hospital early-stage SE, phenytoin in definite SE, propofol in refractory or super-refractory SE. In patients with liver disease, the authors suggest the use of lorazepam as drug of choice in pre-hospital and intra-hospital early-stage SE, lacosamide in definite SE, propofol in refractory or super-refractory SE. A list of preferred drugs for all SE stages is provided.Objective To examine the symptoms experienced and the change in driving habits in individuals with concussion.Materials and methods A survey was created by a team of rehabilitation professionals who see persons with concussion in their clinics. The survey captured demographics, mechanism of injury, date of injury, symptoms experienced during driving, if drivers felt safe when driving, and changes in driving habits since the concussion. Non-parametric tests were used to compare symptoms experienced and driving habits across three groups which were created based on time since injury.Results Of the 140 participants, 74% (104/140) had resumed driving after concussion; of these 27% (28/104) reported that they felt unsafe while driving. Forty-four per cent (46/104) experienced symptoms while driving, of which headache, and difficulty concentrating were the most common symptoms experienced throughout the concussion spectrum (acute to chronic phase). Most drivers (78/104, 75%) with concussion had changed their driving habits by driving less often and shorter distances, and by avoiding nighttime driving and heavy traffic areas.Conclusions Headache and concentration problems were experienced by drivers regardless of the time since injury. Most drivers had made changes to their driving habits. Clinicians should consider the symptom burden patients experience and discuss driving restrictions to ensure driving safety.Lung cancer is a leading cause of cancer death in Canada, and accurate, early diagnosis are critical to improving clinical outcomes. Artificial Intelligence (AI)-based imaging analytics are a promising healthcare innovation that aim to improve the accuracy and efficiency of lung cancer diagnosis. Maximizing their clinical potential while mitigating their risks and limitations will require focused leadership informed by interdisciplinary expertise and system-wide insight. We convened a knowledge exchange workshop with diverse Saskatchewan health system leaders and stakeholders to explore issues surrounding the use of AI in diagnostic imaging for lung cancer, including implementation opportunities, challenges, and priorities. This technology is anticipated to improve patient outcomes, reduce unnecessary healthcare spending, and increase knowledge. However, health system leaders must also address the needs for robust data, financial investment, effective communication and collaboration between healthcare sectors, privacy and data protections, and continued interdisciplinary research to achieve this technology's potential benefits.Background We assessed the safety and immunogenicity of 2 + 1 infant regimens initiated with the 13-valent pneumococcal conjugate vaccine (PCV13) and completed with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV). Methods This partially blinded study randomized 6-12-week-old infants to receive two-dose priming and a booster (at ages 2, 4, 12-15 months) with PCV13 at priming and PHiD-CV at boosting (PPS); PCV13 then PHiD-CV at priming and PHiD-CV at boosting (PSS); or PHiD-CV at priming and boosting (SSS control). All analyses were descriptive, i.e., no statistical significance tests were done. Results The total vaccinated cohort at priming comprised 294 infants. Grade 3 adverse events were reported after 8.7% (PPS), 11.4% (PSS), and 16.9% (SSS) of primary doses (primary objective). No serious adverse events were considered vaccination-related. For most PHiD-CV serotypes, observed percentages of children reaching antibody concentrations ≥0.2 µg/mL and opsonophagocytic activity (OPA) titers above cutoffs were similar across groups 1 month post-priming and post-booster. Observed geometric mean antibody concentrations and OPA titers were lower for some PHiD-CV serotypes with the mixed regimens than with PHiD-CV only, especially for PSS. However, no tests of statistical significance were performed. Conclusions Immunogenicity of the two mixed PCV13/PHiD-CV regimens seemed mostly similar to that of a PHiD-CV-only series, although observed antibody GMCs and OPA GMTs for some PHiD-CV serotypes were lower. No safety concerns were raised. The clinical relevance of the observed differences is unknown. Clinical trial registration ClinicalTrials.gov NCT01641133.Introduction Waldenström Macroglobulinaemia (WM) is a heterogeneous, incurable condition which often relapses after chemoimmunotherapy. Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib. Zanubrutinib is a selective, potent BTK inhibitor with the potential to reduce toxicity and improve efficacy. Areas covered This review examines the activity of Zanubrutinib in treating treatment-naïve and relapsed refractory WM and it's toxicity profile when compared to Ibrutinib. Outcomes from the AU003 and ASPEN studies will be examined in detail including a particular focus on MYD88WT and CXCR4WHIM disease. Strengths and weaknesses of this treatment approach will be highlighted and future directions for research will be identified. Expert opinion Zanubrutinib induces deeper responses and have greater activity in MYD88WT and CXCR4WHIM WM. Zanubrutinib also has a favorable toxicity profile when compared to Ibrutinib.