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Somatoform traits, which manifest as persistent physical symptoms without a clear medical cause, are prevalent and pose challenges to clinical practice. Understanding the genetic basis of these disorders could improve diagnostic and therapeutic approaches. With publicly available summary statistics, we conducted a multivariate genome-wide association study (GWAS) and multi-omic analysis of four somatoform traits-fatigue, irritable bowel syndrome, pain intensity, and health satisfaction-in 799,429 individuals genetically similar to Europeans. Using genomic structural equation modeling, GWAS identified 134 loci significantly associated with a somatoform common factor, including 44 loci not significant in the input GWAS and 8 novel loci for somatoform traits. Gene-property analyses highlighted an enrichment of genes involved in synaptic transmission and enriched gene expression in 12 brain tissues. Six genes, including members of the CD300 family, had putatively causal effects mediated by protein abundance. There was substantial polygenic overlap (76-83%) between the somatoform and externalizing, internalizing, and general psychopathology factors. Somatoform polygenic scores were associated most strongly with obesity, Type 2 diabetes, tobacco use disorder, and mood/anxiety disorders in independent biobanks. Drug repurposing analyses suggested potential therapeutic targets, including MEK inhibitors. Mendelian randomization indicated potentially protective effects of gut microbiota, including Ruminococcus bromii . These biological insights provide promising avenues for treatment development., Competing Interests: Conflicts of Interest: Dr. Kranzler is a member of advisory boards for Dicerna Pharmaceuticals, Sophrosyne Pharmaceuticals, Enthion Pharmaceuticals, Clearmind Medicine, and Altimmune; a consultant to Sobrera Pharmaceuticals; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; and a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the last three years by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi, Otsuka, and Pear Therapeutics; Drs. Gelernter and Kranzler hold U.S. patent 10,900,082 titled: “Genotype-guided dosing of opioid agonists,” issued 26 January 2021.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (n combined  = 898,680). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records as a source of phenotypic information for studying the genetics of TUD., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: Educational initiatives are a sustainable means to address provider shortages in resource-limited settings (RLS), yet few regional anesthesia curricula for RLS have been described. We sought to design a reproducible training model for RLS called Global Regional Anesthesia Curricular Engagement (GRACE), implement GRACE at an RLS hospital in Ghana, and measure training and practice-based outcomes associated with GRACE implementation., Methods: Fourteen of 15 physician anesthesiologists from the study location and three from an outside orthopedic specialty hospital consented to be trainees and trainers, respectively, for this prospective single-center observational study with pre-post evaluations. We conducted an initial needs assessment to determine current clinical practices, participants' learning preferences, and available resources. Needs assessment findings, expert panel recommendations, and investigator consensus were then used to generate a site-specific curriculum that was implemented during two 3-week periods. We evaluated trainee satisfaction and changes in knowledge, clinical skill, and peripheral nerve block (PNB) utilization using the Kirkpatrick method., Results: The curriculum consisted of didactic lectures, simulations, and clinical instruction to teach ultrasound-guided PNB for limb injuries. Pre-post evaluations showed trainees were satisfied with GRACE, median knowledge examination score improved from 62.5% (15/24) to 91.7% (22/24) (p<0.001), clinical examination pass rate increased from 28.6% (4/14) to 85.7% (12/14) (p<0.01), and total PNB performed in 3 months grew from 48 to 118., Conclusions: GRACE applied in an RLS hospital led to the design, implementation, and measurement of a regional anesthesia curriculum tailored to institutional specifications that was associated with positive Kirkpatrick outcomes., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The use of interscalene blocks (ISBs) for shoulder surgery improves postoperative pain control, reduces recovery room times, and reduces overall hospital stays. The most common and potentially disabling adverse effect associated with ISBs is phrenic nerve paresis. Fortunately, persistent phrenic nerve paresis (PPNP) is rare. There are only 4 case reports of PPNP in the English literature. At our institution, we identified 9 cases of PPNP over a 9-year period, representing an incidence of 1 (0.048%) in 2069. In conducting a case-control series, we found that symptomatic cervical spine disease is a risk factor for the development of PPNP. Patients with PPNP had a significantly higher incidence of cervical spine disease (85.7%) compared with the control group (30.9%), P < 0.01. Persistent phrenic nerve paresis remains a perplexing complication of ISB, and many questions remain unanswered. Our data identify an important risk factor that can aid in the risk stratification of patients undergoing ISB.