Inhibition of advanced glycation end product formation and serum protein infiltration in bioprosthetic heart valve leaflets: Investigations of anti-glycation agents and anticalcification interactions with ethanol pretreatment.

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP.

Race, History of Abuse, and Homelessness Are Associated With Forced Medication Administration During Psychiatric Inpatient Care.

OBJECTIVE: Although previous research has suggested that racial disparities exist in the administration of forced medication (FM) in psychiatric inpatients, data remain scarce regarding other contributing variables. Therefore, this study examined sociodemographic and clinical variables associated with FM administration in psychiatric inpatients. METHODS: Electronic medical records from 57,615 patients admitted to an academic psychiatric hospital between 2010 and 2018 were reviewed to identify patients who received FM. These records indicated that FM petitions were requested and approved for ∼6200 patients. Patients were excluded from the analysis if they met the following exclusion criteria: under 18 years of age, presence of intellectual/developmental disability, dementia, or other neurological condition, or primary diagnosis of a nonpsychiatric medical condition or a substance-induced mood or psychotic disorder. After data on those patients were excluded, the final sample included records from 2569 patients (4.5% of the total records) in which the administration of FM was petitioned for and approved. The FM group was compared with a control group of 2569 patients matched in terms of age, sex, and admission date (no-forced medication group; NFM) via propensity scoring matching. Group comparisons (FM vs. NFM group) examined sociodemographic factors (race, age, sex, living situation), clinical features (diagnosis, substance abuse, history of abuse), and outcomes (length of stay, readmission rate). Regression analyses examined the association between FM and sociodemographic, clinical, and outcome variables. RESULTS: Compared with the NFM group, the FM group contained significantly more African Americans (P<0.001), homeless individuals (P<0.001), and individuals with histories of abuse (P<0.001). Having received FM was a significant predictor of a longer length of stay (P<0.001) and higher readmission rates (P<0.001). DISCUSSION: These results suggest that FM is more likely to be instituted in psychiatric inpatients who are of a minority race (African American), are in a homeless living situation, and/or have a history of abuse. Moreover, FM may be associated with poorer clinical outcomes at least as measured by the length of stay and higher readmission rates. We discuss possible reasons for these results and the importance of culturally competent and trauma-focused care.