Leveraging transcriptomics for precision diagnosis: Lessons learned from cancer and sepsis.

Diagnostics require precision and predictive ability to be clinically useful. Integration of multi-omic with clinical data is crucial to our understanding of disease pathogenesis and diagnosis. However, interpretation of overwhelming amounts of information at the individual level requires sophisticated computational tools for extraction of clinically meaningful outputs. Moreover, evolution of technical and analytical methods often outpaces standardisation strategies. RNA is the most dynamic component of all -omics technologies carrying an abundance of regulatory information that is least harnessed for use in clinical diagnostics. Gene expression-based tests capture genetic and non-genetic heterogeneity and have been implemented in certain diseases. For example patients with early breast cancer are spared toxic unnecessary treatments with scores based on the expression of a set of genes (e.g., Oncotype DX). The ability of transcriptomics to portray the transcriptional status at a moment in time has also been used in diagnosis of dynamic diseases such as sepsis. Gene expression profiles identify endotypes in sepsis patients with prognostic value and a potential to discriminate between viral and bacterial infection. The application of transcriptomics for patient stratification in clinical environments and clinical trials thus holds promise. In this review, we discuss the current clinical application in the fields of cancer and infection. We use these paradigms to highlight the impediments in identifying useful diagnostic and prognostic biomarkers and propose approaches to overcome them and aid efforts towards clinical implementation.

Communication is crucial: Lessons from COVID-19 vaccination and pregnancy.

The morbidity and mortality from COVID-19 infection are higher in pregnant women compared to their nonpregnant counterparts. As real-world evidence accumulates demonstrating there is no increased risk of adverse maternal and neonatal outcomes associated with COVID-19 vaccination during pregnancy, guidelines have evolved from a case-by-case benefit-risk decision through to clear recommendation in April 2021 for COVID-19 vaccination in pregnancy. However, vaccine hesitancy is a barrier to uptake, especially among the younger population and individuals of ethnic minority backgrounds; pregnant women have additional concerns. Trust in the importance and effectiveness of the vaccine, trust in public health agencies and science, together with good communication methods regarding the safety of COVID-19 vaccines are strong factors for vaccination acceptance in pregnancy. Lack of trust in the health system was worsened by initial knowledge gaps in the information provided about COVID-19 infection and the safety and immunogenicity of COVID-19 vaccines. This was exacerbated by access to incorrect information and misinformation to fill in those knowledge gaps, especially with the increased use of social media. To provide advice and reassurance on COVID-19 vaccine safety to pregnant women, healthcare professionals involved in their care should have the knowledge and skills to provide risk-benefit communication and would benefit from access to training in science communication. Clinical pharmacologists have the expertise to appraise and synthesize emerging pharmacovigilance data, which can inform and support risk-benefit communication by other clinicians. Information should be strategically directed at individual audiences, taking their perspectives and foundational belief systems into consideration.

HIV: new drugs, new guidelines.

PURPOSE OF REVIEW: This review discusses recent changes in HIV treatment guidelines, focussing on the optimal time for starting antiretroviral therapy (ART) in chronic asymptomatic infection, and treatment options for ART-naïve patients. RECENT FINDINGS: Understanding of HIV pathogenesis has progressed significantly, with a growing appreciation of the role of HIV replication in causing inflammation and promoting both AIDS and non-AIDS diseases. Early suppression of HIV replication with ART benefits the individual, and by reducing transmission and promoting engagement with care also brings public health benefits. For years, efavirenz-based ART was favoured by treatment guidelines, reflecting unsurpassed performance in clinical trials. New treatment options show high efficacy and safety and include single-tablet coformulations for once-daily dosing to improve convenience. Recent data have demonstrated superiority over efavirenz of regimens based on rilpivirine in patients with low pre-ART HIV-1 RNA load and raltegravir or dolutegravir regardless of the viral load. SUMMARY: Some guidelines now recommend starting ART regardless of CD4 cell counts, whereas others take a more cautious approach pending results from studies that are testing the clinical benefit of early therapy. New treatment options allow therapy to be tailored to the patient's circumstances and are suitable for early ART initiation.