Analysis of genomic alterations in cell-free DNA (cfDNA) is evolving as an approach to detect, monitor, and genotype malignancies. Methods to separate the liquid from the cellular fraction of whole blood for circulating tumor DNA (ctDNA) analyses have been largely unstudied, although these may be a critical consideration for assay performance. To evaluate the influence of blood processing on cfDNA and ctDNA quality and yield, we compared the cfDNA levels in serum with those in plasma. Given the limitations of serum for ctDNA analyses, we evaluated the effects of two plasma processing approaches, KEDTA and Cell-Free DNA BCT (BCT) tubes, on cfDNA and ctDNA recovery. A total of 45 samples from nine patients with cancer were collected in both tube types. Once collected, blood was processed into plasma immediately or kept at room temperature and processed into plasma at 1, 3, 5, or 7 days. As early as 24 hours after collection, plasma isolated from blood collected in KEDTA tubes contained an elevated level of cfDNA that increased over time compared with BCT tubes where no significant increase in cfDNA levels was observed. When samples from an additional six patients with cancer, collected in the same manner, were stored at 4°C in KEDTA tubes over the course of 3 days, total cfDNA and ctDNA levels were comparable between samples collected in BCT tubes. At day 3, there was a trend toward a decrease in ctDNA levels in both tubes that was more pronounced when measuring the mutant allele fraction for cases stored at 4°C in KEDTA tubes. In summary, methods of blood processing have a strong influence on cfDNA and ctDNA levels and should be a consideration when evaluating ctDNA in peripheral circulation. .

BACKGROUND:Polymorphisms in the MUC5B promoter, TOLLIP , and nine additional genetic loci have been associated with idiopathic pulmonary fi brosis (IPF) within non-Hispanic white populations. It is unknown whether these variants account for risk of IPF in other racial/ethnic populations. We conducted a candidate single nucleotide polymorphism (SNP) association study in cohorts of Mexican and Korean patients with IPF.

Psoriatic arthritis (PsA) is a multifaceted disease, with a high impact on patients’ psychological and physical well-being. There is increasing recognition that assessment of both clinical aspects of disease and patient identified concerns, such as fatigue, work disability, and treatment satisfaction need to be addressed. Only then can we fully understand disease burden and make well-informed treatment decisions aimed at improving patients’ lives. In recent years, there has been much progress in the development of unidimensional and composite measures of disease activity, as well as questionnaires capturing the patient’s perspective in psoriatic disease. Despite these advances, there remains disagreement amongst clinicians as to which instruments should be used. As a consequence, they are yet to receive widespread implementation in routine clinical practice. This review aims to summarize currently available clinical and patient-derived assessment tools, which will provide clinicians with a practical and informative resource.

Purpose of reviewPsoriatic arthritis (PsA) is a chronic inflammatory spondyloarthritis that can cause progressive joint damage and irreversible disability. Advances in modern therapies, now mean a target of remission is an achievable goal in PsA. There is strong and consistent evidence that a treat-to-target (T2T) approach to PsA management results in better patient outcomes; however, the practicalities of incorporating this strategy into routine clinical practice remain a challenge. The heterogeneous nature of this condition and the need for validated outcome measures have to-date hampered consensus on a definition of remission. This review aims to summarise the current T2T research landscape in PsA and highlight potential roles for biomarkers and imaging advances in revolutionising the T2T concept.Recent findingsThere is a growing body of evidence to support the implementation of a T2T strategy, using a pre-defined target in PsA management, with significant benefits in disease outcome, physical function and quality of life.SummaryWhilst remission is the ultimately goal for PsA patients and their clinicians, further comparative studies of different treatment targets are needed to establish a widely acceptable definition of remission.

Background: The risk factors for prevalent delirium in older hospitalised adults in Sub-Saharan Africa (SSA) remain poorly characterised. Methods: A total of 510 consecutive admissions of adults aged ≥60 years to acute medical wards of Kilimanjaro Christian Medical Centre in northern Tanzania were recruited. Patients were assessed within 24 h of admission with a risk factor questionnaire, physiological observations, neurocognitive assessment, and informant interview. Delirium and dementia diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM V) and DSM IV respectively, by an expert panel. Results: Being male, current alcohol use, dementia, and physiological markers of illness severity were significant independent risk factors for delirium on multivariable analysis. Conclusions: The risk factors for prevalent delirium in older medical inpatients in SSA include pre-existing dementia, and are similar to those identified in high-income countries. Our data could help inform the development of a delirium risk stratification tool for older adults in SSA.

The introduction of biologic disease modifying anti-rheumatic drugs (bMDARDs) have revolutionised the treatment of psoriatic arthritis (PsA). This, combined with a 'treat-to-target' approach, means that achieving remission is increasingly possible. In patients with well-controlled PsA, there is little consensus on whether bDMARDs should be continued, tapered or discontinued altogether. Tapering or discontinuation of bDMARDs could offer significant financial savings and minimise patient burden and unwanted drug-related side effects. However, there is a risk of loss of remission. This primary focus of this paper is to review the current evidence on bDMARD tapering and discontinuation in PsA. We explore the criteria employed by studies to define patients eligible for bDMARD tapering or discontinuation and the process by which this occurs. We also review the outcomes of bDMARD tapering and discontinuation, the predictors, and the likelihood of restoring remission following relapse. To date, bDMARD tapering seems to be feasible and safe in patients with PsA who are in remission or with low disease activity. Lower disease activity and increased duration on tumour necrosis factor inhibitors (TNFi) increases the likelihood of successful bDMARD tapering. In contrast, discontinuing bDMARDs appears to carry a substantial risk of loss of remission. Those with higher disease activity at time of TNFi discontinuation, current smokers, male sex, increased skin involvement, and synovial hypertrophy seen on ultrasound prior to discontinuation are at greater risk of losing remission post bDMARD discontinuation. In those who lose remission, reinstating the standard dose of bDMARD appears to be effective in restoring remission. Key points •In patients with well-controlled psoriatic arthritis on biologics, there is little consensus on whether they should continue on the same dose, taper the dose or discontinue the biologic altogether.• Current evidence is based on small retrospective observational studies, and suggests that biologic tapering is preferable to discontinuation, which carries a substantial risk of loss of remission.• There is a need for high-quality randomised controlled trials to substantiate current evidence in order to guide clinical decision making. If safe and feasible, tapering or discontinuation can result in substantial financial savings and also minimise treatment burden and drug-related side effects for patients.

Both instruments appeared useful for delirium screening in this inpatient setting, but had significant limitations. The combination of assessment items identified may form the basis of a brief, simple delirium screening tool suitable for use by non-specialist clinicians. Further development work is needed.

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