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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The anaesthetist has the option to perform fluid therapy by adhering to strict protocols and rules-of-thumb. However, gaining a better understanding of how to guide this therapy adds interest to the anaesthetist’s professional life, allows more capable handling of tricky situations, and leads to improved patient outcomes. This author has used, and sometimes developed, methods that aim to give the anaesthetist an opportunity to personalize the art and practice of fluid therapy. This chapter includes tips and suggestions about methods that might be considered.
The Best Practices in Social and Behavioral Research Course was developed to provide instruction on good clinical practice for social and behavioral trials. This study evaluated the new course.
Methods
Participants across 4 universities took the course (n=294) and were sent surveys following course completion and 2 months later. Outcomes included relevance, how engaging the course was, and working differently because of the course. Open-ended questions were posed to understand how work was impacted.
Results
Participants rated the course as relevant and engaging (6.4 and 5.8/7 points) and reported working differently (4.7/7 points). Participants with less experience in social and behavioral trials were most likely to report working differently 2 months later.
Discussion
The course was perceived as relevant and engaging. Participants described actions taken to improve rigor in implementing trials. Future studies with a larger sample and additional participating sites are recommended.
Fully updated and expanded, the second edition of Clinical Fluid Therapy in the Perioperative Setting brings together the world's leading experts in fluid management to explain what you should know when providing infusion fluids to surgical and critical care patients. Current evidence-based knowledge, essential basic science, and modern clinical practice are explained in 34 focused and authoritative chapters. New chapters cover topics such as burn injury, monitoring of the microcirculation, the glycocalyx layer, intensive care, trauma, transplantations, and adverse effects of infusion fluids. Each chapter begins with an abstract, providing a quick overview of the topic, followed by detailed clinical and pre-clinical guidance. Together, the chapters guide the reader in the use of fluid therapy in all aspects of perioperative patient care. Edited by Robert G. Hahn, a clinical anesthesiologist and highly experienced researcher in fluid therapy, this is essential reading for all anesthesiologists, intensivists, and surgeons.