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Objective: Language used by providers in medical documentation may reveal evidence of race-related implicit bias. We aimed to use natural language processing (NLP) to examine if prevalence of stigmatizing language in emergency medicine (EM) encounter notes differs across patient race/ethnicity., Methods: In a retrospective cohort of EM encounters, NLP techniques identified stigmatizing and positive themes. Logistic regression models analyzed the association of race/ethnicity and themes within notes. Outcomes were the presence (or absence) of 7 different themes: 5 stigmatizing (difficult, non-compliant, skepticism, substance abuse/seeking, and financial difficulty) and 2 positive (compliment and compliant)., Results: The sample included notes from 26,363 unique patients. NH Black patient notes were less likely to contain difficult (odds ratio (OR) 0.80, 95% confidence interval (CI), 0.73-0.88), skepticism (OR 0.87, 95% CI, 0.79-0.96), and substance abuse/seeking (OR 0.62, 95% CI, 0.56-0.70) compared to NH White patient notes but more likely to contain non-compliant (OR 1.26, 95% CI, 1.17-1.36) and financial difficulty (OR 1.14, 95% CI, 1.04-1.25). Hispanic patient notes were less likely to contain difficult (OR 0.68, 95% CI, 0.58-0.80) and substance abuse/seeking (OR 0.78, 95% CI, 0.66-0.93). NH NA/AI patient notes had twice the odds as NH White patient notes to contain a stigmatizing theme (OR 2.02, 95% CI, 1.64-2.49)., Conclusions: Using an NLP model to analyze themes in EM notes across racial groups, we identified several inequities in the usage of positive and stigmatizing language. Interventions to minimize race-related implicit bias should be undertaken., (© 2024. W. Montague Cobb-NMA Health Institute.)

Purpose: Chemotherapy-induced diarrhea (CID) is a relatively common adverse event in the treatment of patients with colorectal cancer. The LAR for Chemotherapy-Induced Diarrhea (LARCID) trial evaluated the efficacy and safety of long-acting release octreotide (octreotide LAR) for the prevention of CID in this population., Patients and Methods: Patients with colorectal cancer starting adjuvant or first-line treatment with a chemotherapy combination containing fluorouracil, capecitabine, and/or irinotecan were randomly assigned to receive octreotide LAR 30 mg intramuscularly every 4 weeks (experimental arm) or the physician's treatment of choice in case of diarrhea (control arm)., Results: A total of 139 patients were randomly assigned, most of whom received fluorouracil- and oxaliplatin-containing chemotherapy regimens. The rate of diarrhea was 76.1% in the experimental group (n = 68) and 78.9% in the control group (n = 71). Treatment with octreotide LAR did not prevent or reduce the severity of CID. Treatment choices for diarrhea management included loperamide in the majority of patients. No benefit from octreotide LAR was identified in terms of need for diarrhea treatment, opioids, or intravenous hydration or in the rate of hospitalization or quality of life., Conclusion: This study could not prove the efficacy of octreotide LAR in the prevention of CID.

Purpose: This study evaluated the effects of oral capecitabine on the quality of life (QOL) of Brazilian patients with metastatic colorectal cancer who received capecitabine (1000 or 1250 mg/m2 twice a day on days 1-14, every 3 weeks) in a prospective, multicenter, open-label, noncomparative study., Patients and Methods: Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires before cycle 1, at weeks 7 and 13, and at the end of treatment. In total, 1437 patients (mean age, 59.6 years [+/- 13.5 years]) were enrolled., Results: In women, statistically significant improvements were observed in 6 QLQ-C30 and 6 QLQ-CR38 domains (QLQ-C30: emotional function, nausea/ vomiting, pain, constipation, financial problems, and body image; QLQ-CR38: future perspective, micturition problems, defecation problems, stoma-related problems, weight loss and global health status). In men, statistically significant improvements were observed in 8 QLQ-C30 and 5 QLQ-CR38 domains (QLQ-C30: emotional function, social function, pain, insomnia, appetite loss, constipation, financial problems, and future perspective; QLQ-CR38: micturition problems, defecation problems, stoma-related problems, weight loss, and global health status). Statistically significant worsening of sexual function/enjoyment occurred in both sexes., Conclusion: Overall, 59%-86% of patients maintained or improved QOL during capecitabine therapy.

Oligonucleotide-directed mutagenesis was utilized to investigate the requirement of tryptophan residues located in the N-terminal domain of the glucagon-like peptide-1 (GLP-1) receptor for the ability to bind its ligand and to induce cAMP generation. W39, W72, W87, W91, W110, and W120 were mutated into alanine. Two of the six tryptophan residues, W72 and W110, are highly conserved within the receptor subfamily. After transfection of mutated cDNAs in COS-7 or CHL cells, it appeared that mutant W87 A bound [125I] GLP-1 with the same affinity as wild-type receptor and induced signal transduction to a comparable extent. In contrast, mutant receptors W39A, W72A, W91A, W110A, and W120A lost the ability to bind [125I] GLP-1. Because all mutated receptor cDNAs were transcribed on RNA level (Northern blot) and the receptor proteins were expressed at the plasma membrane level (Western blot), it is concluded that with the exception of W87 all trytophan residues are essential for receptor ligand interaction. This indicates the significance of hydrophobic interactions within the N-terminal domain of the GLP-1 receptor.

The proglucagon-derived glucagon-like peptide-1 (GLP-1) secreted by the L-cells exerts an insulinotropic effect at pancreatic beta-cells. The GLP-1 receptor belongs to a new subfamily of the superfamily of seven transmembrane, G-protein-coupled receptors (7 TM receptors). We show that a single point mutation within a nonconserved motif of the N-terminal, extracellular domain of the GLP-1 receptor results in a dramatic impairment of receptor function. Thus, substitution of W39 by A or F is followed by a loss of GLP-1 binding. Exchange of K38 with A (mutant K) slightly decreased GLP-1 binding affinity. Replacement of the negatively charged Q37 by K and K38 by A, which is identical with a shift of the positively charged K one position upstream, resulted in a receptor mutant able to bind GLP-1 with higher affinity as the wild-type receptor and mutant K. Therefore, the presence of an imidazol ring structure in the investigated receptor region is necessary for an intact receptor function Furthermore, a positive charge at this location is important for the receptor-ligand interaction.

GLP-1 (glucagon-like peptide 1 (7-36) amide) plays an important role in the regulation of insulin secretion and proinsulin gene expression of pancreatic beta-cells. Patients with insulinoma tumors show uncontrolled insulin hypersecretion. This study demonstrates the molecular cloning of a cDNA for the GLP-1 receptor from a human insulinoma employing a lambda-gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 463 amino acids which showed high homology to the GLP-1 receptor in normal human pancreas. Four amino acid exchanges were found in comparison to a receptor sequence obtained from regular pancreatic islets. When transfected transiently into COS-7 or stably into fibroblast CHL cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under GLP-1 stimulation. The receptor accepted GLP-1 and the non-mammalian agonist exendin-4 as high affinity ligands. In transfected COS-7 cells, GLP-1 did not influence intracellular calcium, whereas in the stably transfected fibroblasts GLP-1 transiently increased intracellular calcium to a small extent. The understanding of GLP-1 receptor regulation and signal transduction will aid in the discovery of compounds that act as agonists of the GLP-1 receptor for potential use in the treatment of diabetes and will facilitate the understanding of its expression under normal and pathophysiological conditions.

The mineral contents of Na, K, Ca, Mg, Cl and P was determined in different batches of 5 preterm formulas. The purpose of this study was 1st to investigate whether the analytical data are in agreement with the specifications of the manufactures and 2nd whether there are large variations between different batches of the same formula. For each analyzed mineral we found marked differences between the specifications and our measurements in at least one of the formulas. In these cases the differences between the labels and the medians of the analytical data were larger than half of the range of all determinations of the respective formula. Without exception the mean values for K were all clearly lower than the specifications of the producers. In 4 of the 5 premature formulas variation coefficients greater than 10% were observed for at least one mineral. The results show that coincidental variations of mineral contents in different batches can result in a disadvantageous mineral composition because of synergistic effects on metabolism. In this context the importance of the sum of Na and K over Cl in premature formulas is stressed with regard to renal acid excretion. The introduction of more stringent quality standards is proposed.