ABSTRACT
BACKGROUND: Clozapine levels can be influenced by many factors, including pharmacogenomic variability, pharmacokinetic drug interactions, and infection/inflammation. The concentration-to-dose ratio (C/D), a measure of a medication's rate of metabolism and clearance, may increase during an acute infection due to decreased medication metabolism and clearance. CASE REPORT: A 56-year-old White man was restarted on clozapine and titrated up to 350 mg/d with therapeutic steady-state levels (C/D 1.11) on hospital day (HD) 69. At this time, he was also being treated for COPD exacerbation. For the next month, he continued to complain of cough, but vital signs and chest x-ray remained normal. Labs were unremarkable except for occasional leukocytosis that would resolve on repeat evaluation. A routine clozapine level drawn on HD 104, resulted on day 108 and showed clozapine toxicity with C/D 4.05, although the patient was asymptomatic. After receipt of labs on day 109, showing elevated WBC count, he was immediately sent to the emergency room where he was admitted for treatment of pneumonia. On return to the state hospital, the patient was continued on 100 mg clozapine and titrated to 200 mg/d based on low drug levels. He continued to do well on 200 mg/d clozapine with C/D averaging 1.13 (range, 0.75-1.52). DISCUSSION: Acute infection and illness can lead to significantly increased clozapine levels and toxicity, even if symptoms of toxicity are minimal or absent. This appears to be the first report of a toxic level being the first indication of severe medical illness.
ABSTRACT
PURPOSE: Controversy remains within the pediatric urology community regarding adequate duration of followup after hypospadias repair. Some have suggested that minimal long-term followup is necessary due to a low incidence of late complications. The objective of this study was to delineate time to complication detection for primary hypospadias repairs. MATERIALS AND METHODS: We queried our prospectively maintained hypospadias database and identified all patients undergoing primary hypospadias repair from June 2007 to June 2018. Patients were excluded if they had undergone primary repair elsewhere or did not have a followup visit. Complications were defined by the need for an additional unplanned surgical procedure. Kaplan-Meier analysis was performed to assess time to complication by degree of hypospadias. RESULTS: A total of 1,280 patients met inclusion criteria, of whom 976 (68.9%) underwent distal, 64 (4.9%) mid shaft and 240 (18.8%) proximal hypospadias repair. Complication rates were 10.7% (104 patients), 18.8% (12) and 53.8% (129, p<0.0001) for distal, mid shaft and proximal hypospadias repair, respectively. Only 47% of complications were detected within the first year postoperatively. Median time to complication for all repair types was 69.2 months (IQR 23 to 131.9), ie 83.1 months (IQR 42.0 to 131) for patients undergoing distal repair and 29.4 months (IQR 11.9 to 82.1) for patients undergoing proximal repair (p <0.001). CONCLUSIONS: In our large single institution series of pediatric patients undergoing hypospadias repair fewer than half of the complications presented within the first year postoperatively. Long-term followup is recommended for patients undergoing hypospadias repair to adequately detect and address complications.
