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Deep learning approaches have tremendous potential to improve the predictive power of traditional suicide prediction models to detect and predict intentional self-harm (ISH). Existing research is limited by a general lack of consistent performance and replicability across sites. We aimed to validate a deep learning approach used in previous research to detect and predict ISH using clinical note text and evaluate its generalizability to other academic medical centers. We extracted clinical notes from electronic health records (EHRs) of 1,538 patients with International Classification of Diseases codes for ISH and 3,012 matched controls without ISH codes. We evaluated the performance of two traditional bag-of-words models (i.e., Naïve Bayes, Random Forest) and two convolutional neural network (CNN) models including randomly initialized (CNNr) and pre-trained Word2Vec initialized (CNNw) weights to detect ISH within 24 hours of and predict ISH from clinical notes 1-6 months before the first ISH event. In detecting concurrent ISH, both CNN models outperformed bag-of-words models with AUCs of.99 and F1 scores of 0.94. In predicting future ISH, the CNN models outperformed Naïve Bayes models with AUCs of 0.81-0.82 and F1 scores of 0.61-.64. We demonstrated that leveraging EHRs with a well-defined set of ISH ICD codes to train deep learning models to detect and predict ISH using clinical note text is feasible and replicable at more than one institution. Future work will examine this approach across multiple sites under less controlled settings using both structured and unstructured EHR data.

Genome-wide association studies (GWAS) have successfully identified over two hundred thousand genotype-trait associations. Yet some challenges remain. First, complex traits are often associated with many single nucleotide polymorphisms (SNPs), most with small or moderate effect sizes, making them difficult to detect. Second, many complex traits share a common genetic basis due to ‘pleiotropy’ and and though few methods consider it, leveraging pleiotropy can improve statistical power to detect genotype-trait associations with weaker effect sizes. Third, currently available statistical methods are limited in explaining the functional mechanisms through which genetic variants are associated with specific or multiple traits. We propose multi-GPA-Tree to address these challenges. The multi-GPA-Tree approach can identify risk SNPs associated with single as well as multiple traits while also identifying the combinations of functional annotations that can explain the mechanisms through which risk-associated SNPs are linked with the traits. First, we implemented simulation studies to evaluate the proposed multi-GPA-Tree method and compared its performance with existing statistical approaches. The results indicate that multi-GPA-Tree outperforms existing statistical approaches in detecting risk-associated SNPs for multiple traits. Second, we applied multi-GPA-Tree to a systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and to a Crohn’s disease (CD) and ulcertive colitis (UC) GWAS, and functional annotation data including GenoSkyline and GenoSkylinePlus. Our results demonstrate that multi-GPA-Tree can be a powerful tool that improves association mapping while facilitating understanding of the underlying genetic architecture of complex traits and potential mechanisms linking risk-associated SNPs with complex traits.

IntroductionBoth the quadratus lumborum block (QLB) and the pericapsular nerve group (PENG) block provide effective postoperative analgesia after hip surgery while minimizing the impact on motor function. This study aimed to compare QLB and PENG in patients undergoing primary total hip arthroplasty (THA).MethodsThis superiority trial randomized patients scheduled for elective THA to receive a lateral QLB or a PENG with a lateral femoral cutaneous nerve (LFC) block for postoperative analgesia. Perioperative analgesic protocols were standardized. The primary outcome was postoperative cumulative opioid consumption measured over time up to 72 hours. Secondary outcomes included postoperative pain scores in the first 72 hours, time to ambulation, length of stay, and patient-reported functional outcome measures (Hip disability and Osteoarthritis Outcome Score for Joint Replacement and Patient-Reported Outcome Measures Information System-10 scores).ResultsThis trial consented and randomized 106 subjects and 101 were included in the analysis: PENG (n=50), QLB (n=51). Mean (95% CI) opioid consumption in intravenous morphine milligram equivalents differed at 36 hours (mean difference (95% CI), 18.0 (0.80, 35.1); p=0.040), 48 hours (23.0 (5.20, 40.8); p=0.011), 60 hours (28.0 (9.24, 46.7); p=0.004), and 72 hours (33.0 (13.0, 53.0); p=0.001). There were no significant differences between treatment arms in average resting pain score, time to ambulation, rate of same-day discharge, length of stay, or patient-reported functional outcomes.ConclusionWhile both lateral QLB and PENG block+LFC block are effective analgesic methods for patients undergoing THA, patients receiving lateral QLB had decreased cumulative opioid consumption from 36 to 72 hours postoperative and lower pain scores with movement compared with patients receiving PENG+LFC blocks.Trial registration numberNCT05710107.

Preoperative gastric ultrasound allows non-invasive qualitative and quantitative assessment of gastric contents aiding in preoperative risk assessment. We hypothesized that appropriately fasted diabetic surgical patients taking GLP-1 agonists would have higher gastric volumes than those not taking GLP-1 agonists. This prospective, observational cohort study enrolled diabetic patients undergoing elective surgery, comparing those taking (n = 106) and not taking (n = 100) GLP-1 agonists. The primary outcome was gastric volume assessed via gastric ultrasound in the right lateral decubitus position. Secondary outcomes included presence of a full stomach (solids/thick liquids or greater than 1.5 mL/kg clear liquid), need for surgery delay, Perlas grade, and occurrence of intraoperative aspiration. The impact of GLP-1 agonist type, duration of use, and timing of last dose on gastric volume was also examined. Diabetic patients on GLP-1 agonists had significantly higher median gastric volumes compared to patients not on GLP-1 agonists (0.61 mL/kg vs 0.16 mL/kg, P < 0.001) and increased odds of a full stomach (OR 11.3, 95 % CI 5.2–24.7, P < 0.0001). GLP-1 agonist use correlated with higher Perlas grades (P < 0.001). Gastric volumes were significantly higher with GLP-1 agonist use within 7 days of surgery relative to use within 7–14 days or more than 14 days from surgery (P < 0.001 for both comparisons). GLP-1 agonist therapy was associated with higher residual gastric volumes and higher risks of full stomachs in fasted diabetic patients. GLP-1 agonist use within 7 days of surgery was also associated with higher gastric volumes relative to holding therapy for over 7 days, supporting current consensus-based guidelines. •GLP-1 agonist therapy was associated with higher residual gastric volumes.•Higher gastric volumes seen with cessation of GLP-1 agonists within 7 days of surgery.•No difference in gastric volumes when holding GLP-1 agonists 7–14 days and > 14 days.•This opposes consensus-based guidelines on preoperative cessation of GLP-1 agonists.

Exposure to Endocrine Disrupting Chemicals (EDC) has been linked with several adverse outcomes. In this review, we examine EDCs that are pervasive in the environment and are of concern in the context of human, animal, and environmental health. We explore the consequences of EDC exposure on aquatic life, terrestrial animals, and humans. We focus on the exploitation of genomics technologies and in particular whole transcriptome sequencing. Genome-wide analyses using RNAseq provides snap shots of cellular, tissue and whole organism transcriptomes under normal physiological and EDC perturbed conditions. A global view of gene expression provides highly valuable information as it uncovers gene families or more specifically, pathways that are affected by EDC exposures, but also reveals those that are unaffected. Hypotheses about genes with unknown functions can also be formed by comparison of their expression levels with genes of known function. Risk assessment strategies leveraging genomic technologies and the development of toxicology databases are explored. Finally, we review how the Adverse Outcome Pathway (AOP) has exploited this high throughput data to provide a framework for toxicology studies.

BackgroundReports of clinical improvement following mesenchymal stromal cell (MSC) infusions in refractory lupus patients at a single centre in China led us to perform an explorative phase I trial of umbilical cord derived MSCs in patients refractory to 6 months of immunosuppressive therapy.MethodsSix women with a SLEDAI >6, having failed standard of care therapy, received one intravenous infusion of 1×106 MSCs/kg of body weight. They maintained their current immunosuppressives, but their physician was allowed to adjust corticosteroids initially for symptom management. The clinical endpoint was an SRI of 4 with no new British Isles Lupus Activity Guide (BILAG) As and no increase in Physician Global Assessment score of >0.3 with tapering of prednisone to 10 mg or less by 20 weeks.ResultsOf six patients, five (83.3%; 95% CI 35.9% to 99.6%) achieved the clinical endpoint of an SRI of 4. Adverse events were minimal. Mechanistic studies revealed significant reductions in CD27IgD double negative B cells, switched memory B cells and activated naïve B cells, with increased transitional B cells in the five patients who met the endpoint. There was a trend towards decreased autoantibody levels in specific patients. Two patients had increases in their Helios+Treg cells, but no other significant T cell changes were noted. GARP-TGFβ complexes were significantly increased following the MSC infusions. The B cell changes and the GARP-TGFβ increases significantly correlated with changes in SLEDAI scores.ConclusionThis phase 1 trial suggests that umbilical cord (UC) MSC infusions are very safe and may have efficacy in lupus. The B cell and GARP-TGFβ changes provide novel insight into mechanisms by which MSCs may impact disease.Trial registration numberNCT03171194.

PurposeSeveral observational studies have presented conflicting results on the association between the use of proton pump inhibitors (PPIs) or histamine H2 receptor antagonist (H2RA) and the risk of coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis aimed to examine this association.MethodsIn July 2021, PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for articles investigating the relationship between the two main acid suppressants and COVID-19. Studies showing the effect estimates as hazard ratio (HR) for severe outcomes or incidence of COVID-19 were evaluated using a random-effects model.ResultsA total of 15 retrospective cohort studies with 18,109 COVID-19 cases were included in the current meta-analysis. PPI use was significantly associated with severe outcomes of COVID-19 (hazard ratio [HR] = 1.53; 95% confidence interval [CI]: 1.20–1.95) but not with the incidence of COVID-19, whereas H2RA use was significantly associated with decreased incidence (HR = 0.86, 95% CI: 0.76–0.97). For subgroup analyses of PPIs, increased severe outcomes of COVID-19 were observed in < 60 years, active use, in-hospital use, and Asians. For subgroup analyses of H2RAs, decreased severe outcomes of COVID-19 were observed in > 60 years, while in-hospital use and use in Asia were associated with higher disease severity.ConclusionsClose observation can be considered for COVID-19 patients who use PPIs to prevent severe outcomes. However, caution should be taken because of substantial heterogeneity and plausible protopathic bias.

BackgroundElectrical storm can be challenging to treat, requiring a multidisciplinary team to coordinate medical management and invasive procedures. As the stellate ganglion provides efferent sympathetic outflow to the myocardium, stellate ganglion blocks (SGB) can be used to combat ventricular arrhythmias that arise from sympathetic overactivity. Data are scarce regarding SGB catheters as a treatment for electrical storm. We reviewed our use of SGB catheters for refractory electrical storm using our pathway collaboratively developed by critical care, cardiology, and regional anesthesia teams.MethodsWe conducted a retrospective cohort study of patients who underwent an SGB for electrical storm between January 2020 and April 2022 in our cardiovascular intensive care unit. The primary outcome was the sustained cessation of electrical storm for 24 hours.ResultsUpon chart review, 27 patients were identified and 11 met inclusion criteria. Cessation of electrical storm for 24 hours was achieved in 90% (n=10) of patients after left SGB. Similarly, 90% (n=10) had no documented episodes of ventricular arrhythmias requiring intervention within 6 hours after SGB.ConclusionsSGBs can interrupt or treat electrical storm. SGB catheters allow for prolonged arrhythmia cessation without repeated blocks and decrease the risk of repeat episodes of ventricular arrhythmias.