The Application of Genetic Risk Scores in Rheumatic Diseases: A Perspective.

Modest effect sizes have limited the clinical applicability of genetic associations with rheumatic diseases. Genetic risk scores (GRSs) have emerged as a promising solution to translate genetics into useful tools. In this review, we provide an overview of the recent literature on GRSs in rheumatic diseases. We describe six categories for which GRSs are used: (a) disease (outcome) prediction, (b) genetic commonalities between diseases, (c) disease differentiation, (d) interplay between genetics and environmental factors, (e) heritability and transferability, and (f) detecting causal relationships between traits. In our review of the literature, we identified current lacunas and opportunities for future work. First, the shortage of non-European genetic data restricts the application of many GRSs to European populations. Next, many GRSs are tested in settings enriched for cases that limit the transferability to real life. If intended for clinical application, GRSs are ideally tested in the relevant setting. Finally, there is much to elucidate regarding the co-occurrence of clinical traits to identify shared causal paths and elucidate relationships between the diseases. GRSs are useful instruments for this. Overall, the ever-continuing research on GRSs gives a hopeful outlook into the future of GRSs and indicates significant progress in their potential applications.

Changes in comorbid depression following intensive trauma-focused treatment for PTSD and complex PTSD.

BACKGROUND: The extent to which intensive trauma-focused treatment for individuals with post-traumatic stress disorder (PTSD) is also effective in treating comorbid major depressive disorder (MDD) remains unclear. OBJECTIVE: The purpose of the present study was to test the hypothesis that brief intensive trauma-focused therapy for PTSD is associated with significant reductions in depressive symptoms and loss of diagnostic status of MDD. METHODS: A total of 334 adult patients with PTSD (189 patients who were also diagnosed with MDD) underwent a brief intensive trauma-focused treatment programme consisting of EMDR therapy, prolonged exposure, physical activity, and psychoeducation. At pre-treatment, post-treatment and 6-month follow-up, severity and diagnostic status of PTSD and MDD were assessed. A linear mixed model was used to analyze changes in the severity of PTSD and depressive symptoms, whereas a generalized linear mixed model was used to determine changes in the MDD diagnostic status. RESULTS: Treatment resulted in a significant and strong decrease of PTSD and MDD symptoms at post-treatment (d = 2.34 and 1.22, respectively), and at 6-month follow-up (d = 1.67 and 0.73, respectively). The proportion of patients fulfilling the diagnostic status of MDD changed from 57% at pre-treatment to 33% at the 6-month follow-up. Although the initial response to treatment did not differ between patients with and without comorbid MDD, for both groups a significant relapse in depressive symptoms was found after six months, which could be explained almost entirely by the presence of CPTSD at baseline. CONCLUSIONS: The results support the notion that brief, intensive trauma-focused treatment is highly effective for individuals with PTSD and comorbid MDD. Because patients with CPTSD are vulnerable to relapse in depressive symptoms, this target group may require additional treatment.

Intensive trauma-focused treatment (ITFT) of PTSD proved to be associated with a significant decrease in comorbid MDD.Comorbid MDD did not moderate the effect of ITFT for PTSD.Presence of Complex PTSD was predictive of relapse of MDD symptoms 6 months later.

Precision cancer medicine: Concepts, current practice, and future developments.

Precision cancer medicine is a multidisciplinary team effort that requires involvement and commitment of many stakeholders including the society at large. Building on the success of significant advances in precision therapy for oncological patients over the last two decades, future developments will be significantly shaped by improvements in scalable molecular diagnostics in which increasingly complex multilayered datasets require transformation into clinically useful information guiding patient management at fast turnaround times. Adaptive profiling strategies involving tissue- and liquid-based testing that account for the immense plasticity of cancer during the patient's journey and also include early detection approaches are already finding their way into clinical routine and will become paramount. A second major driver is the development of smart clinical trials and trial concepts which, complemented by real-world evidence, rapidly broaden the spectrum of therapeutic options. Tight coordination with regulatory agencies and health technology assessment bodies is crucial in this context. Multicentric networks operating nationally and internationally are key in implementing precision oncology in clinical practice and support developing and improving the ecosystem and framework needed to turn invocation into benefits for patients. The review provides an overview of the diagnostic tools, innovative clinical studies, and collaborative efforts needed to realize precision cancer medicine.