Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.

RATIONALE: Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined. OBJECTIVES: To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients. METHODS: We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors. RESULTS: Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (ß = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (ß = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction. CONCLUSIONS: This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients.

Support to caregivers who have received genetic information about neurodevelopmental and psychiatric vulnerability in their young children: A narrative review.

Diagnosis of pathogenic genetic variants associated with neurodevelopmental and psychiatric disorders (NPDs) is increasingly made early in life. This narrative review focuses on the need for, and provision of, psychological supports following genetic diagnosis. We conducted a literature search of publications on how caregivers are informed about the NPD vulnerability associated with genetic variants, challenges and unmet needs when receiving this information, and whether psychological supports are provided. Given its early recognition, the 22q11.2 deletion has been studied thoroughly for two decades, providing generalizable insights. This literature indicates the complex caregivers' needs related to learning about potential NPD vulnerabilities associated with a genetic variant, include how to communicate the diagnosis, how to identify early signs of NPDs, how to deal with stigma and a lack of medical expertise outside of specialized genetics clinics. With one exception, no publications describe psychotherapeutic support provided to parents. In the absence of support, caregivers struggle with several unmet needs regarding potential longer-term NPD implications of a genetic diagnosis. The field needs to go beyond explaining genetic diagnoses and associated vulnerabilities, and develop approaches to support caregivers with communicating and managing NPD implications across the child's lifespan.

Endometrial Cancer Surgery for Elderly Women--The Early Postoperative Period.

OBJECTIVE: The aim of this study was to examine the early postoperative period and assess whether elderly patients recuperate differently than do their younger counterparts after surgery for endometrial cancer. METHODS: This retrospective chart review comprised all women older than 75 years who underwent laparotomy for endometrial cancer staging at our center from January 2005 through December 2010 and a consecutive control group of women younger than 74 years. Parameters included demographic variables, surgical procedure/findings, postoperative morbidity, and pathology. RESULTS: Ninety patients older than 75 years and 88 younger patients were identified. The elderly patients had a statistically significant prolonged wait for bowel movement (5.9 vs 3.1 days, P = 0.002) and ambulated later (4.1 vs 1.1 days, P < 0.001). Postoperative hospital stay was similar in both groups (5.8 vs 4.2 days, P = 0.37). Early postoperative complications (fever, bowel, wound, eventration, cardiopulmonary) occurred at a similar rate in both groups. CONCLUSIONS: Elderly patients after laparotomy for endometrial cancer staging ambulated later and recovered bowel function later than did the younger patients. This did not translate into prolonged hospital stay or excessive complications. Earlier intervention with physical therapy and stool softeners can possibly close this gap in recovery.